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Old 05-30-2013, 01:35 PM
Dross Dross is offline
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Default Immune system to fight brain tumors

Research at Lund University in Sweden gives hope that one of the most serious types of brain tumour, glioblastoma multiforme, could be fought by the patients' own immune system. The tumours are difficult to remove with surgery because the tumour cells grow into the surrounding healthy brain tissue. A patient with the disease therefore does not usually survive much longer than a year after the discovery of the tumour. The team has tested different ways of stimulating the immune system, suppressed by the tumour, with a 'vaccine'.

The vaccine is based on tumour cells that have been genetically modified to start producing substances that activate the immune system. The modified tumour cells (irradiated so that they cannot divide and spread the disease) have been combined with other substances that form part of the body's immune system. The treatment has produced good results in animal experiments: 75 per cent of the rats that received the treatment were completely cured of their brain tumours. "Human biology is more complicated, so we perhaps cannot expect such good results in patients. However, bearing in mind the poor prognosis patients receive today, all progress is important", said doctoral student Sara Fritzell, part of the research group led by consultant Peter Siesjö. She has previously tested combining the activation of the immune system with chemotherapy.

When the chemotherapy was applied directly to the tumour site, the positive effects reinforced each other, and a huge 83 per cent of the mice survived. "Our idea is in the future to give patients chemotherapy locally in conjunction with the operation to remove as much of the tumour as possible", said Sara Fritzell. Peter Siesjö is currently applying for permission to carry out a clinical study on stimulation of the immune system – with or without local chemotherapy – as a treatment for patients with glioblastoma multiforme.

Last edited by gdpawel : 06-03-2013 at 12:43 PM. Reason: posted full article on forum
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Old 06-03-2013, 12:41 PM
gdpawel gdpawel is offline
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Default Dendritic Cell Vaccine For Relapsed Neuroblastoma?

One year after his last treatment, a six-year-old boy with recurrent neuroblastoma is in complete remission for his high-risk metastatic cancer. Doctors reported this case study in the January 2013 issue of Pediatrics, the journal of the American Academy of Pediatrics, which was funded in part by a joint grant from the Andrew McDonough B+ Foundation, Pierce Phillips Charity and Solving Kids' Cancer.

Current treatments for high-risk neuroblastoma patients include chemotherapy, radiation therapy, surgery, stem cell transplant, and immunotherapy. Less than half of the children survive in spite of the intensive and toxic standard therapy. Long term survival after a relapse is less than 5%.

Previous clinical trials in adult solid tumors have successfully used cancer-specific targets (NY-ESO-1, MAGE-A1, and MAGE-A3) to kill cancer cells. Now, scientists at the University of Louisville have used these same targets for neuroblastoma by creating a vaccine that causes the body's own immune system to attack the tumor cells. Dendritic cells are immune cells collected from the patient and grown in cultures after they are exposed to specific antigens. The dendritic cells "teach" the patient's T-cells to seek out and kill the cancer cells after they are returned to the patient through a series of injections.

Cancer treatment vaccines differ from other vaccines in that they treat active cancers or help to prevent recurrence. The principal investigator for this study, Kenneth Lucas, M.D., is the division chief of Pediatric Hematology-Oncology and Stem Cell Transplantation at the University of Louisville Department of Pediatrics. The funding provided critical support to further Dr. Lucas' ongoing work to find new treatments for neuroblastoma and other deadly childhood cancers.

In the case study, one year after the patient's last vaccination, the tumors cells that were located in the boy's bone marrow disappeared and he now shows no evidence of disease.

The study includes children with sarcomas as well as neuroblastoma, and will be completed in 2013.

For patients with relapsed neuroblastoma, there are few promising treatment options in clinical trials. More effective and less toxic treatments are desperately needed.

"This research builds on five years of pre-clinical research, which identified three new immunological targets that are specific to this pediatric cancer," said Scott Kennedy, the Executive Director of Solving Kids' Cancer. "The case study highlights the potential therapeutic progress that can be made against neuroblastoma, and brings hope to patients and their families in finding a lasting cure."

Citation: Solving Kids' Cancer. "Complete Remission Induced By Dendritic Cell Vaccine For Relapsed Neuroblastoma Patient." Medical News Today. MediLexicon, Intl., 31 Jan. 2013

Immunological Research: A multi-faceted approach to curing disease

Gregory D. Pawelski

Last edited by gdpawel : 06-08-2013 at 12:10 PM. Reason: additional info
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Old 06-12-2013, 12:44 PM
gdpawel gdpawel is offline
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Default Understanding Immunotherapy

Immunotherapy (also called biologic therapy or biotherapy) is a type of cancer treatment designed to boost the body's natural defenses to fight the cancer. It uses materials either made by the body or in a laboratory to improve, target, or restore immune system function. Although it is not entirely clear how immunotherapy treats cancer, it may work by stopping or slowing the growth of cancer cells, stopping cancer from spreading to other parts of the body, or helping the immune system increase its effectiveness at eliminating cancer cells.

There are several types of immunotherapy, including monoclonal antibodies, non-specific immunotherapies, and cancer vaccines.

Monoclonal antibodies

When the body’s immune system detects antigens (harmful substances, such as bacteria, viruses, fungi, or parasites), it produces antibodies (proteins that fight infection). Monoclonal antibodies are made in a laboratory, and when they are given to patients, they act like the antibodies the body produces naturally. Monoclonal antibodies are given intravenously (through a vein) and work by targeting specific proteins on the surface of cancer cells or cells that support the growth of cancer cells. When monoclonal antibodies attach to a cancer cell, they may accomplish the following goals:

Allow the immune system to destroy the cancer cell.

The immune system doesn't always recognize cancer cells as being harmful. To make it easier for the immune system to find and destroy cancer cells, a monoclonal antibody can mark or tag them by attaching to specific parts of cancer cells that are not found on healthy cells.

Prevent cancer cells from growing rapidly.

Chemicals in the body called growth factors attach to receptors on the surface of cells and send signals that tell the cells to grow. Some cancer cells make extra copies of the growth factor receptor, which makes the cancer cells grow faster than normal cells. Monoclonal antibodies can block these receptors and prevent the growth signal from getting through.

Deliver radiation directly to cancer cells.

This treatment, called radioimmunotherapy, uses monoclonal antibodies to deliver radiation directly to cancer cells. By attaching radioactive molecules to monoclonal antibodies in a laboratory, they can deliver low doses of radiation specifically to the tumor while leaving healthy cells alone. Examples of these radioactive molecules include ibritumomab tiuxetan (Zevalin) and tositumomab (Bexxar).

Diagnose cancer.

Monoclonal antibodies carrying radioactive particles may also help diagnose certain cancers, such as colorectal, ovarian, and prostate cancers. Special cameras identify the cancer by showing where the radioactive particles accumulate in the body. In addition, a pathologist (a doctor who specializes in interpreting laboratory tests and evaluating cells, tissues, and organs to diagnose disease) may use monoclonal antibodies to determine the type of cancer a patient may have after tissue has been removed during a biopsy.

Carry powerful drugs directly to cancer cells.

Some monoclonal antibodies carry other cancer drugs directly to cancer cells. Once the monoclonal antibody attaches to the cancer cell, the cancer treatment it is carrying enters the cell, causing the cancer cell to die without damaging other healthy cells. Brentuximab vedotin (Adcetris), a treatment for certain types of Hodgkin and non-Hodgkin lymphoma, is one example.

Other monoclonal antibodies approved by the U.S. Food and Drug Administration (FDA) to treat cancer include:

Bevacizumab (Avastin)
Alemtuzumab (Campath)
Cetuximab (Erbitux)
Trastuzumab (Herceptin)
Rituximab (Rituxan)
Panitumumab (Vectibix)
Ofatumumab (Arzerra)

Side effects of monoclonal antibody treatment are usually mild and are often similar to an allergic reaction. Possible side effects include rashes, low blood pressure, and flu-like symptoms, such as fever, chills, headache, weakness, extreme tiredness, loss of appetite, upset stomach, or vomiting.

Although monoclonal antibodies are considered a type of immunotherapy, they are also classified as a type of targeted treatment (a treatment that specifically targets faulty genes or proteins that contribute to cancer growth and development). Learn more about targeted treatments.

Non-specific immunotherapies

Like monoclonal antibodies, non-specific immunotherapies also help the immune system destroy cancer cells. Most non-specific immunotherapies are given after or at the same time as another cancer treatment, such as chemotherapy or radiation therapy. However, some non-specific immunotherapies are given as the main cancer treatment.

Two common non-specific immunotherapies are:

Interferons. Interferons help the immune system fight cancer and may slow the growth of cancer cells. An interferon made in a laboratory, called interferon alpha (Roferon-A [2a], Intron A [2b], Alferon [2a]), is the most common type of interferon used in cancer treatment. Side effects of interferon treatment may include flu-like symptoms, an increased risk of infection, rashes, and thinning hair.

Interleukins. Interleukins help the immune system produce cells that destroy cancer. An interleukin made in a laboratory, called interleukin-2, IL-2, or aldesleukin (Proleukin), is used to treat kidney cancer and skin cancer, including melanoma. Common side effects of IL-2 treatment include weight gain and low blood pressure, which can be treated with other medications. Some people may also experience flu-like symptoms.

Cancer vaccines

A vaccine is another method used to help the body fight disease. A vaccine exposes the immune system to a protein (antigen) that triggers the immune system to recognize and destroy that protein or related materials. There are two types of cancer vaccines: prevention vaccines and treatment vaccines.

Prevention vaccine. A prevention vaccine is given to a person with no symptoms of cancer to prevent the development of a specific type of cancer or another cancer-related disease. For example, Gardasil is a vaccine that prevents a person from being infected with the human papillomavirus (HPV), a virus known to cause cervical cancer and some other types of cancer. It was the first FDA-approved vaccine for cancer. Cervarix is another vaccine that is approved to prevent cervical cancer in girls and women. Learn more about HPV vaccination for cervical cancer and the role of HPV in other cancers. In addition, the U.S. Centers for Disease Control and Prevention recommends that all children should receive a vaccine that prevents infection with the hepatitis B virus, which may cause liver cancer.

Treatment vaccine. A treatment vaccine helps the body's immune system fight cancer by training it to recognize and destroy cancer cells. It may prevent cancer from coming back, eliminate any remaining cancer cells after other types of treatment, or stop cancer cell growth. A treatment vaccine is designed to be specific, which means it should target the cancerous cells without affecting healthy cells. At this time, sipuleucel-T (Provenge) is the only treatment vaccine approved in the United States. It is designed for treating metastatic prostate cancer.

Source: Cancer.Net
Gregory D. Pawelski
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Old 11-27-2013, 10:48 AM
gdpawel gdpawel is offline
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Default Novel new immuno-therapy for malignant brain tumors

Glioblastoma is one of the most ominous brain tumors. Despite aggressive surgery, radiation and chemotherapy the outcome of this disease is almost always fatal. A UZH research team has now achieved success with a novel form of treatment that involves encouraging the body's own immune system to recognise and eliminate cancer cells in the brain.

Animal experiments show that it is relatively easy to treat cancer in the early stages. However, it is far more difficult to successfully treat advanced cancer. Treatment of brain tumors is particularly challenging because regulatory T-cells accumulate in brain tumors and suppress an immune attack.

In several steps using a new strategy and a novel drug, Burkhard Becher's team from the Institute of Experimental Immunology at the University of Zurich has now succeeded in doing exactly this in the case of glioblastoma, one of the most dangerous brain tumors. First step, they stimulated the body's own immune system in such a way that it recognised and then killed the brain tumor cells even in advanced stages of the disease.

The initial objective of their new study was to break through the tumor's protective shield. "We wanted to establish whether we can actually elicit an immune response to a tumor growing within the brain", explains Burkhard Becher. To this end, the team used the immune messenger substance, Interleukin-12. When Interleukin-12 is produced in the tumor, immune cells are stimulated locally in such a manner that the tumor is attacked and rejected. Once this procedure had worked well in the early stages of the tumor, the researchers waited in the next stage until the tumor was very large and the life expectancy of the untreated test animals was less than three weeks. "We only began treatment when it was, in fact, already too late", says the first author of the study Johannes vom Berg. The success rate was low, Berg adds. "We then injected biopharmaceutical Interleukin-12 into the large brain tumor. This did induce an immune response but only led to tumor rejection in one-quarter of the animals."

From 25 to 80 percent: combined treatment leads to success

The researchers were successful when they drew on a new development in skin cancer treatment. They combined intra-tumoral Interleukin-12 treatment with the intravenous administration of a novel immunostimulating drug that suppresses the regulatory T-cells. The rejection of the tumor then worked in 80 percent of the test animals. "I have rarely seen such convincing data in preclinical glioma treatment", says Michael Weller, neurooncologist and Director of the Clinic for Neurology at the University Hospital Zurich. He added, "That's why this development should be tested as soon as possible in clinical trials."

In a joint trial, the team then tested the treatment in a further tumor model which mimics the clinical situation of the brain tumor patient even better. And once again they were successful.

The next step: a clinical trial as soon as possible

The findings of the current research work have been published in the Journal of Experimental Medicine. Their promising results do not mean that the treatment can already be as effective in brain tumor patients. This has to be examined in the next phase for which the team now actively seek commercial partners. Burkhard Becher puts it like this, "We are cautiously optimistic but it's time that we adopted completely new strategies to really get to grips with this fatal tumor."

References: Johannes vom Berg, Melissa Vrohlings, Sergio Haller, Aladin Haimovici, Paulina Kulig, Anna Sledzinska, Michael Weller, and Burkhard Becher. Intratumoral IL-12 combined with CTLA-4 blockade elicits T cell–mediated glioma rejection. The Journal of Experimental Medicine (JEM). November 25, 2013.doi: 10.1084/jem.20130678


Citation: University of Zurich. "Novel new immuno-therapy for malignant brain tumors." Medical News Today. MediLexicon, Intl., 27 Nov. 2013.
Gregory D. Pawelski
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Old 12-26-2013, 11:13 PM
gdpawel gdpawel is offline
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Default Promising results for personalized brain tumor vaccine

New research details an experimental vaccine that could help improve the survival of patients with a lethal brain tumor called glioblastoma mutiforme, compared with standard care alone. This is according to a study published in the journal Neuro-Oncology.

According to the American Association of Neurological Surgeons, glioblastoma mutiforme (GBM) accounts for around 15% of all brain tumors, with onset being most common between the ages of 45 and 70.

The study researchers, led by Orin Bloch of the Northwestern Memorial Hospital in Chicago, say the tumors often become resistant to standard treatments, and median survival from recurrent GBM tumors is approximately 3 to 9 months.

"We are talking about fast-growing tumors that invade normal brain tissue and are very difficult to treat," says Bloch. "These tumors occur in up to 23,000 Americans annually, and are typically treated with surgical resection of the tumor followed by chemotherapy and radiation treatment."

Vaccine tailored to each patient

With these factors in mind, the researchers set out to test a vaccine against the cancer. They note that at present, there are a number of vaccines available for cancer treatment, but none of these are approved for use against GBMs.

The vaccine, called heat-shock peptide protein complex-96 (HSPPC-96), is developed specific to each patient using their own resected tumor tissue.

The investigators say the vaccine works by prompting an immune system response unique to each patient, which sets out to kill any remaining tumor cells following surgery.

Promising results

In a phase II trial, the researchers tested the vaccine on 41 adult patients who had recurrent tumors between 2007 and 2011. Every patient received six does of the HSPPC-96 vaccine.

On monitoring the patients at 6 months after treatment, 90% were still alive, while 30% were alive after 1 year.

Bloch says that studies such as this are vital, because current treatment methods do not stop GBMs from returning. He adds:

"The grim prognosis is exactly why new research is important. GBMs have been around for a long time, and still outcomes are poor. With studies such as this one, I believe we can change that."

Further research needed before approval

Although these results are promising, the investigators say further research is needed before the vaccine can be approved to treat recurrent brain tumors.

Their next step is to conduct a randomized phase II trial to determine whether the HSPPC-96 vaccine is safer and more effective when used alongside avastin - a drug that is standard therapy for recurrent GBM and one known to reduce tumor size.

Commenting on their research, Andrew Parsa, of the Northwestern Feinburg School of Medicine and one of the study authors, says:

"When it comes to brain tumor research, I picture our Northwestern Medicine team climbing a mountain and with every new discovery that shows the potential to prolong survival, we are establishing a new base camp.

Someday, thanks to studies like this one, we'll get to the top of the mountain and convert this particular cancer into a chronic disease - something that patients can live with, controlled by medication."

Reference: Heat-shock protein peptide complex–96 vaccination for recurrent glioblastoma: a phase II, single-arm trial, doi: 10.1093/neuonc/not203, Orin Bloch, Courtney A. Crane, Yelena Fuks, Rajwant Kaur, Manish K. Aghi, Mitchel S. Berger, Nicholas A. Butowski, Susan M. Chang, Jennifer L. Clarke, Michael W. McDermott, Michael D. Prados, Andrew E. Sloan, Jeffrey N. Bruce and Andrew T. Parsa, published in Neuro-Oncology, 12 December 2013.

Citation: Whiteman, Honor. "Promising results for personalized brain tumor vaccine." Medical News Today. MediLexicon, Intl., 19 Dec. 2013

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Old 02-21-2014, 02:03 PM
gdpawel gdpawel is offline
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Default New paradigm in cancer immunotherapy

Tumor metastasis is the primary cause of mortality in cancer patients and remains the major challenge for cancer therapy. Researchers from the Institute of Molecular Biotechnology (IMBA) of the Austrian Academy of Sciences (OeAW) in Vienna have now revealed a novel mechanism by which immune cells can spontaneously reject metastatic tumors. Their findings provide a proof-of-principle that it might be possible to develop a "pill" that awakens the immune system to kill cancer metastases.

The immune system is not only responsible for controlling infections, but also for recognizing and destroying cancer cells. Cancer immunotherapy has therefore become one of the breakthroughs in tumor treatment. Austrian scientists, in collaboration with researches in Australia and Germany, have now shown that a molecule called Cbl-b acts as a molecular brake for Natural Killer (NK) cells to reject cancer. Deletion or targeted inactivation of Cbl-b efficiently enhanced the anti-tumor function of NK cells. As a result the progression of metastases in melanoma and breast cancer was significantly inhibited.

Receptor inhibition unleashes NK cells to kill tumor cells

The researchers also identified a molecular path by which Cbl-b blocks NK cell activity towards metastatic tumors. In collaboration with researchers at the Lead Discovery Centre of the Max Planck Society in Germany, they developed an inhibitor molecule directed against the receptors that are regulated by Cbl-b in NK cells, the so called TAM-receptors. "Cbl-b/TAM constitutes an inhibitory pathway for NK cell activation. Blocking TAM receptors via different routes of administration, including giving it as an oral 'pill', markedly reduced metastatic spreading in our model systems", says Magdalena Paolino, first author of the study. Last author Josef Penninger explains: "Metastases are the main reason why cancer patients die. Our results hold promise that it might be possible to develop Cbl-b or TAM inhibitors that empowers the innate immune system to kill cancer metastases. This would be indeed opening the Holy Grail for cancer therapy. However, more research needs to be conducted to advance our findings and to test for possible side-effects."

Solving a mystery in metastases control

Along the way, the researchers also solved a more than 50 year old puzzle in cancer treatment. It has been known for decades that warfarin, the most widely used anticoagulant worldwide, reduces tumor metastasis in model systems. However, the underlying mechanisms remained unclear. "Our findings provide a molecular explanation for this old paradoxon, revealing that warfarin has anti-metastatic effects through inhibiting the novel identified Cbl-b/TAM receptor pathway in NK cells. This also offers the possibility to re-assess the use of vitamin K antagonists such as warfarin in cancer therapy", concludes Magdalena Paolino.

Era of Immunotherapy

Every day, multiple cells in our body become transformed and develop the potential to become cancer cells. However, such tumor cells display unusual antigens that are either inappropriate for the cell type or its environment, and can thus be recognized by the body's immune system. Modern medicine therefore aims to stimulate the patient's immune system to attack the tumor cells. In light of recent findings and future promises, cancer immunotherapy has even been chosen as scientific breakthrough of the year 2013 by the renowned journal Science. The findings made by IMBA scientists now provide evidence that one can find key molecular brakes in innate immune cells that, when modified, allow such cells to seek out and destroy metastatic tumors.

Citation: Institute of Molecular Biotechnology. "New paradigm in cancer immunotherapy." Medical News Today. MediLexicon, Intl., 19 Feb. 2014.
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Old 03-27-2014, 02:31 PM
gdpawel gdpawel is offline
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Default Killing cancer cells with radiotherapy makes immunotherapy more effective?

Radiation therapy fights cancer in more ways than one. Not only does it force cancer cells to self-destruct, but several studies demonstrate that it also activates the immune system to attack tumor cells. This activation can be used to boost current immunotherapies, such as anti-tumor vaccines, to produce better clinical results. What's less clear, however, is exactly how to combine the two therapies to get the best bang for the therapeutic buck.

To address this question, researchers at Thomas Jefferson University tested an experimental cancer vaccine in combination with radiation therapy in mice with colorectal cancer. In research publishing online March 24th in the International Journal of Radiation Oncology, they showed that the vaccine was most effective when tumors were irradiated first and then vaccinated a week later.

"Prior to these experiments, we didn't appreciate the impact that sequencing of these treatments had on their combined ability to generate immune and clinical responses," says Thomas Jefferson University radiation oncologist Matthew Witek M.D., first author of the study. "Remarkably, immune activation and tumor regression only occurred when radiation was given prior to vaccination."

When mice received either treatment alone, the researchers noticed only a modest reduction in tumor size. However, when radiation was given first, the investigators saw a six-fold increase in cancer-fighting immune cells, and impressively, complete remission of the majority of tumors.

Although the work will need to be reproduced in humans to determine if the same holds true for cancer patients, the finding is exciting, says lead researcher Adam Snook, Ph.D., an instructor in the department of Pharmacology and Experimental Therapeutics. "In a patient population that will undergo radiation therapy as standard treatment, these results provide a roadmap to amplifying the effects of immunotherapies like the one we're developing for colon cancer."

Targeted Diagnostics & Therapeutics, Inc, which provided research funding that, in part, supported this work, has a license to commercialize inventions related to this work. The authors report no other conflict of interest.


This work was supported by grants from the National Institutes of Health (RC1 CA146033, P30 CA56036, R01 CA170533), the Pennsylvania Department of Health (SAP #4100059197, SAP #4100051723), and Targeted Diagnostic and Therapeutics Inc. The Pennsylvania Department of Health specifically disclaims responsibility for any analyses, interpretations, or conclusions.

M. Witek, et al., "Tumor radiotherapy creates therapeutic vaccine response to the colorectal cancer antigen GUCY2C" International Journal of Radiation Oncology, 2014.

Citation: Thomas Jefferson University. "First treat tumors with radiotherapy to directly kill cancer cells, making immunotherapy more effective." Medical News Today. MediLexicon, Intl., 26 Mar. 2014.
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Old 06-23-2015, 09:22 AM
gdpawel gdpawel is offline
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Default Investigational Brain Cancer Vaccine Produces Strong Immunological Response

Investigational Brain Cancer Vaccine Produces Strong Immunological Response

Phase I clinical trial results of SurVaxM presented at AACR Annual Meeting 2015 in Philadelphia

A first-of-its kind cancer vaccine, SurVaxM, has demonstrated safety and tolerability in patients with recurrent or progressive malignant brain tumors, according to results of a phase I study conducted by Roswell Park Cancer Institute (RPCI) researchers. The findings were presented at the American Association for Cancer Research Annual Meeting 2015, being held April 18-22 in Philadelphia.

The study title is “Phase I study of SurVaxM in patients with survivin-expressing recurrent malignant gliomas” (CT301; section 24, poster board 1). This immunotherapeutic vaccine will now be evaluated in a larger phase II clinical trial to assess its effectiveness for patients with advanced brain tumors and a new phase I clinical trial for multiple myeloma patients.

“This recently completed clinical trial was the critical first step for the survivin vaccine, to show its safety for use in humans,” says the study’s senior author, Robert Fenstermaker, MD, Chair of the Department of Neurosurgery and Director of the Neuro-Oncology Program. “Through this process we also confirmed that the vaccine produces a strong immune response and gave us a signal of potential clinical responses.”

Fenstermaker and colleagues entered nine patients with survivin-positive recurrent glioblastoma (brain tumors) who received a series of up to four injections of SurVaxM at two-week intervals. Most patients developed T cell and antibody responses to survivin, the vaccine target. The average expected survival time for recurrent glioblastoma patients is approximately only seven months when receiving standard therapy. In this trial of SurVaxM, six of the eight patients with recurrent glioblastoma have had progressive disease, although five of these survived from 12 to 20-plus months. Two of the eight patients were still progression-free at 20 and 31-plus months.

Survivin is associated with aggressive cancers and an indicator of poor prognosis and response to conventional therapy. The SurVaxM vaccine is designed to target cancer cells that use this protein.

“SurVaxM is on the forefront of the next generation of cancer therapy. By harnessing the body’s own immune system to fight cancer using immunotherapy, we believe we can give hope to patients diagnosed with malignant gliomas and other cancers,” adds the study’s first author, Michael Ciesielski, PhD, Assistant Professor of Oncology in the Department of Neurosurgery at Roswell Park.

About Roswell Park Cancer Institute (RPCI)

The mission of Roswell Park Cancer Institute (RPCI) is to understand, prevent and cure cancer. Founded in 1898, RPCI is one of the first cancer centers in the country to be named a National Cancer Institute-designated comprehensive cancer center and remains the only facility with this designation in Upstate New York. The Institute is a member of the prestigious National Comprehensive Cancer Network, an alliance of the nation’s leading cancer centers; maintains affiliate sites; and is a partner in national and international collaborative programs. For more information, visit [url]

Source: Roswell Park Cancer Institute (RPCI)
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Old 06-23-2015, 09:27 AM
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Default New City Of Hope Immune System Clinical Trial

New City Of Hope Clinical Trial Harnesses The Power Of The Immune System To Fight Brain Cancers

Duarte, CA --(BUSINESS WIRE)--

Already pioneers in the use of immunotherapy, City of Hope researchers are now testing the bold approach to cancer treatment against one of medicine’s biggest challenges: brain cancer. This month, they will launch a clinical trial using patients’ own modified T cells to fight advanced brain tumors.

One of but a few centers in the United States offering human studies in chimeric antigen receptor or CAR–T cell therapy, City of Hope is the only center investigating CAR-T cells in injection form administered directly to brain tumors. In this first-in-humans study, patients with advanced brain tumors will receive injections – directly at the tumor site – of immune cells genetically modified to recognize certain markers on cancer cells.

“The data from our preclinical studies makes us confident that this treatment has the potential to be very powerful and last longer than previous attempts at immunotherapy for brain cancer,” said Benham Badie, M.D., chief of neurosurgery at City of Hope. “This could take the treatment of brain tumors to the next level, and open up a new avenue of treatment to patients who badly need it.”

The safety trial will evaluate the therapy in patients with inoperable glioblastomas and advanced gliomas and in those who have had their tumors surgically removed. The goal is to determine a safe therapeutic dose.

City of Hope has been offering CAR-T cell immunotherapy in clinical trials for several blood cancers. This trial will extend the exciting therapeutic approach to the fight against solid tumors.

T cells are cells in the immune system that recognize threats to the body, then mount an attack. Because cancer can hide from the immune system, CAR-T cell therapy modifies a patient’s T cells to recognize cancer cells. First, a sample of a patient’s T cells are extracted, then genetically modified to recognize receptors on cancer cells.

This City of Hope trial will use a type of T cell known as memory T cells, meaning they replicate in the body and “remember” diseases they’ve fought previously. These memory cells give rise to “soldier” T cells that fight disease. The hope is that the immune system will mount an attack on the existing cancer – then do the same should the cancer recur.

The CAR-T cell laboratory is overseen by Christine Brown, Ph.D., associate director of the T Cell Therapeutics Research Laboratory, and Stephen J. Forman, M.D., Francis & Kathleen McNamara Distinguished Chair in Hematology and Hematopoietic Cell Transplantation.

“CAR-T cell therapy has significant potential to fight not just blood and bone marrow cancers, but a wide range of diseases for which patients need better treatment,” Forman said. “City of Hope is committed to maximizing the potential of this revolutionary therapy for the sake of patients here and around the world.”

The research is being funded through grants from the California Institute of Regenerative Medicine and the Gateway for Cancer Research Foundation.

For more information or to schedule an interview with Badie, contact Media Specialist Denise Heady at 626-218-8803 or by e-mail at [email]

About City of Hope

City of Hope is an independent research and treatment center for cancer, diabetes and other life-threatening diseases. Designated as a comprehensive cancer center, the highest recognition bestowed by the National Cancer Institute, City of Hope is also a founding member of the National Comprehensive Cancer Network, with research and treatment protocols that advance care throughout the nation. City of Hope’s main hospital is located in Duarte, California, just northeast of Los Angeles, with clinics in Antelope Valley and South Pasadena. It is ranked as one of "America's Best Hospitals" in cancer by U.S. News & World Report. Founded in 1913, City of Hope is a pioneer in the fields of bone marrow transplantation and genetics.
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Old 12-28-2016, 06:37 PM
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Default CAR T Cells Produce Dramatic Remission in Glioblastoma

Medscape Medical News

Chimeric antigen receptor (CAR)–modified T-cell therapies have already achieved great success in hematologic malignancies, with clinical trial data showing high complete response rates in leukemia and lymphoma. So far, however, there has been little success with this approach in solid tumors.

Now a case report indicates dramatic remission in a patient with recurrent and rapidly progressing glioblastoma.

The case is described in a brief report published December 29 in the New England Journal of Medicine. Treatment with CAR T-cell therapy led to a transient, complete response in a patient with recurrent multifocal glioblastoma, with dramatic improvements in quality of life, including the discontinuation of use of systemic glucocorticoids and a return to normal life activities. The remission was sustained for 7.5 months, although the patient subsequently developed new tumors.

"This study provides proof-of-principle data that...establish that CAR T cells can mediate profound antitumor activity against a difficult-to-treat solid tumor," the authors conclude.

In a statement, senior coauthor Behnam Badie, MD, chief of neurosurgery at City of Hope, Duarte, California, noted that this type of treatment has tremendous potential and is a "game changer" in how brain tumors may be treated in the future.

"I believe these recent results show we have a potential breakthrough treatment that may have a remarkable impact on patients with malignant brain tumors," Dr Badie said.

Different Target, Local Administration

The CAR T cells that have been used in hematologic malignancies have in the main been focussed on targeting CD19, which is expressed on B cells.

In the latest report, the researchers at the City of Hope developed another type of CAR T cells that target the high-affinity IL-13 receptor IL13Rα2, which is overexpressed in a majority of glioblastomas.

They administered the therapy locally in the brain by directly injecting it into the tumor site and/or through infusion in the ventricular system. (By contrast, for hematologic malignancies, the CAR T cells are administered by intravenous infusion.)

This method of administration was associated with a much lower incidence of adverse events, which have been life-threatening in some of the patients with hematologic malignancies.

In the glioblastoma patient treated with CAR T cells administrated intraventricullarly, the team reports that there was a significant increase in a number of inflammatory cytokines in the cerebrospinal fluid. This increase appeared to correspond with the incidence of grade 1 and 2 symptoms, such as fever, fatigue, and myalgia. The cytokine levels returned to near baseline levels between weekly treatment cycles.

They also note that these immunologic changes were restricted to the cerebrospinal fluid; no notable increases in levels of cytokines and no CAR+ T cells were detectable in the peripheral blood.

"The absence of systemic toxic effects is particularly noteworthy given the severe cytokine release syndrome and neurotoxicity that are often associated with antitumor responses against high disease burden in patients receiving CD19-targeted CAR T-cell therapy," the authors comment.

The patient described in the case report was a 50-year old man who presented with glioblastoma in the right temporal lobe. The patient received standard-of-care therapy that included tumor resection, radiation therapy, and temozolomide (Temodar, Merck & Co).

Six months after his diagnosis, there was evidence of disease recurrence, and he was enrolled into the phase 1 study of IL13Rα2-targeted CAR T cells.

While the experimental therapy was being manufactured, the patient participated in another clinical trial at a different institution. His disease continued to rapidly progress, and he subsequently developed multifocal leptomeningeal glioblastoma involving both cerebral hemispheres.

The patient underwent surgery. Three of the five intracranial tumors that were progressing were resected. These included the largest tumor, which was in the right temporal-occipital region, and two tumors in the right frontal lobe. Two smaller tumors in the left temporal lobe were not removed.

The patient then received CAR T cell therapy at an initial intraventricular infusion of 2 x 106 CAR+ T cells followed by five infusions of 10 x 106 CAR+ T cells, along with weekly intracavitary infusions into the cavity of the resected largest tumor via a catheter device. The patient was assessed after the third and sixth infusions.

During treatment, the patient developed two new lesions, which emerged near the previously resected frontal-lobe tumors. In addition, the two nonresected tumors continued to progress, and new metastatic lesions developed in the patient's spine, causing numbness in his legs.

The researchers felt that delivering treatment into the cerebrospinal fluid would improve their access to sites with multifocal disease, and a second catheter device was placed in the right lateral ventricle. This decision enabled the patient to receive 10 additional intraventricular treatment cycles at 1- to 3-week intervals.

Dramatic Responses

Multiple infusions of CAR T cells were administered over 220 days through two intracranial delivery routes. These infusions were delivered directly into the resected tumor cavity and were delivered into the ventricular system.

The researchers report that after the first three intraventricular infusions (on day 133), they "observed a dramatic reduction in the size of all intracranial and spinal tumors, and after the fifth intraventricular infusion (on day 190), all tumors had decreased by 77% to 100%."

The patient received five additional intraventricular infusions (cycles 12 through 16). During this consolidation phase, all lesions continued to resolve. They were not measurable by MRI and remained undetectable with positron-emission tomography scanning.

What was most remarkable, note the authors, is that after the intraventicular delivery of CAR T cells, all metastatic tumors in the spine resolved. Dexamethasone was also gradually eliminated during intraventricular treatment (day 108 through day 284), and the patient returned to his normal daily life, including returning to work.

The dramatic clinical response was sustained for 7.5 months following the initiation of CAR T-cell therapy, and none of the initial tumors (tumors 1 through 7 and spinal tumors) recurred.

Unfortunately, the patient experienced a recurrence after cycle 16 (228 days after the first CAR T-cell treatment), but at four new locations that were "distinct and nonadjacent to tumors 1 through 7 and the spinal tumors," the researchers emphasize.

They are currently investigating the reasons for the recurrence. Preliminary results suggest decreased expression of IL13Rα2.

The study was funded by grants from Gateway for Cancer Research, the US Food and Drug Administration, the California Institute for Regenerative Medicine, the CIRM Alpha Stem Cell Clinics Network, the National Cancer Institute, and the National Institute of Neurological Disorders and Stroke of the National Institutes of Health. Dr Badie and several coauthors received grant support from Gateway for Cancer Research during the conduct of the study. Three coauthors received grants and other support from Mustang Bio, Inc, and royalties from pending patents related to CARs licensed to Mustang Bio. Coauthor Michael Jensen, MD, has received support and personal fees from Juno Therapeutics, Inc, outside the submitted work, and is named on a patent related to a CAR therapeutic licensed to Juno.

N Engl J Med. 2016;375:2561-9.

Ciitation: CAR T Cells Produce Dramatic Remission in Glioblastoma Medscape Medical News Roxanne Nelson December 28, 2016
Gregory D. Pawelski
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