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SU2C Helps Fight Cancer with Immunotherapy

Posted on June 21, 2016, 1:30 PM

An update on advances in immunotherapy from our friends at the American Association for Cancer Research, SU2C’s Scientific Partner.

Stand Up To Cancer is in the thick of one of the most exciting developments in cancer research and treatment today:  immunotherapy.  This approach involves using highly sophisticated medical interventions to enable the body’s own immune system to fight cancer cells. In recent scientific reports, exciting research by SU2C-supported scientists is helping to move immunotherapy forward so that more patients can benefit.

One of the great success stories in the field is chimeric antigen receptor-modified T-cell (CAR-T cell) therapy, in which the patient’s blood cells are genetically modified and multiplied in the laboratory, then infused intravenously back into the patient’s body to fight the cancer. The therapy works extraordinarily well in many cases of leukemia, often achieving complete remission, but it frequently triggers a serious immune reaction known as cytokine release syndrome (CRS). This “cytokine storm” can make patients very ill and can be life-threatening with symptoms ranging from fever and muscle pain to a drop in blood pressure, difficulty breathing, and kidney failure, among others. While drug treatment can relieve CRS after it develops, better understanding, earlier intervention, and improved management of CRS are critically important for patients undergoing CAR-T cell therapy.

Researchers from the SU2C-St. Baldrick’s Foundation Pediatric Dream Team participated in a recent study that identified signals, called biomarkers, that can be measured in patients’ blood and could predict, with remarkable accuracy, which patients will go on to encounter severe CRS after treatment with CAR-T.  The findings, which were predominately from pediatric patients, could help predict which patients are likely to develop severe CRS and guide management of treatment for childhood, as well as adult leukemia, including early administration of medication to limit CRS and smooth the patient’s recovery. The team published its data in Cancer Discovery, a leading journal published by the American Association for Cancer Research, and hopes to test approaches to catch CRS in the early phase in clinical trials. 

Immunotherapy has also been effective in treatment of metastatic melanoma, although many patients do not respond.  A team of scientists, including the co-leader of the SU2C-Cancer Research Institute (CRI) Immunology Dream Team, felt that a combination of immunotherapies, each of which had limited success in this disease when used alone, might succeed where the single therapies failed. They were right. In a newly released first-in-human study, the team combined an adoptive cell therapy, in which patients are treated with their own natural cancer-fighting immune cells after they are collected and grown in large numbers in the laboratory, with checkpoint blockade therapy, in which drugs are used to ”release the brakes” that cancer cells insidiously place on the patient’s anti-cancer immunity. The researchers treated just 10 patients with the combination treatment; seven of them responded. Two fortunate patients, one of whom had melanoma that had reached stage 3 despite surgery and previous immunotherapies, saw their disease go into complete remission that has lasted for years. The strategy may hold “broad promise” for development of immunotherapy against melanoma, the researchers wrote in the Journal of Experimental Medicine.  They also published results from a related study in the Journal of Clinical Oncology.

SU2C–supported research gives hope that immunotherapy, which has already produced great success in leukemia and melanoma, can be improved and expanded even further. The researchers whose work is described above include among other authors four members of the SU2C-St. Baldrick’s Dream Team at Children’s Hospital of Philadelphia (Stephan A. Grupp, David T. Teachey, David M. Barrett, and Shannon L. Maude); Cassian Yee of The University of Texas MD Anderson Cancer Center, co-leader of the SU2C-CRI Immunology Dream Team; and Jedd D. Wolchok of Memorial Sloan Kettering Cancer Center, former member of the SU2C-CRI Immunology Dream Team and current co-leader of another SU2C Dream Team. 

For further reading, abstracts of the articles are:

Identification of Predictive Biomarkers for Cytokine Release Syndrome after Chimeric Antigen Receptor T-cell Therapy for Acute Lymphoblastic Leukemia, by David T. Teachey, et al., Cancer Discovery, June 2016. FREE ARTICLE available at: http://cancerdiscovery.aacrjournals.org/content/6/6/664.full

Forecasting Cytokine Storms with New Predictive Biomarkers, by Rayne H. Rouce and Helen E. Heslop, Cancer Discovery, June 2016. http://cancerdiscovery.aacrjournals.org/content/6/6/579.abstract

Combined IL-21–primed polyclonal CTL plus CTLA4 blockade controls refractory metastatic melanoma in a patient, by Aude G. Chapuis, et al., Journal of Experimental Medicine, May 30, 2016. http://jem.rupress.org/content/early/2016/05/24/jem.20152021.abstract?sid=811857bc-f0b5-4a9f-a766-5ea80cebb555

T-Cell Therapy Using Interleukin-21–Primed Cytotoxic T-Cell Lymphocytes Combined With Cytotoxic T-Cell Lymphocyte Antigen-4 Blockade Results in Long-Term Cell Persistence and Durable Tumor Regression. Aude G. Chapuis, et al., Journal of Clinical Oncology, June 6, 2016.  http://jco.ascopubs.org/content/early/2016/06/02/JCO.2015.65.5142

 


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