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Being able to identify targets for adoptive cell therapies is one of the first steps in developing personalized treatments for people with difficult-to-treat cancer. However, it can be difficult to predict whether a patient will have an immune response to a particular abnormal protein caused by mutations and who will serve as a new antigen (neoantigen). Using ultra-sensitive, high-throughput isolation technology (called imPACT Isolation Technology®) designed to isolate specific T cells from neoepitopes, UCLA researchers have been able to characterize and identify neo-antigens at the same time. 39, origin of antitumor responses in a patient treated with anti-PD. 1 blocks and isolates T cell receptors responsible for this effect.
The use of immune control point inhibitors to treat people with metastatic melanoma has helped transform the treatment of people with the most deadly skin cancer. Despite its success, many people do not benefit from treatment. Until now, adoptive cell therapy, which involves extracting and harvesting T cells from a patient and manipulating them in the laboratory, targeted common antigens. This limits many people potentially treated with therapy because not all cancers have the same antigen as the one to be targeted. The researchers are working to improve methods of identifying new targets for these therapies in the hope of developing more effective and personalized therapies.
The researchers badyzed T cell responses in two patients with advanced melanoma, one responding to anti-PD1 treatment and the other not responding to treatment. Using samples taken before and during treatment, the team isolated T cells by specifically recognizing tumor mutations using the IMPACT Isolation Technology technology developed by PACT Pharma. The technology allows researchers to identify T cells and their receptors, capable of detecting mutations. After identifying T cell receptors, they were reintroduced into peripheral blood T cells using a non-viral genome engineering method to generate new neo-antigen-specific T cells used to kill cells. melanoma of the same patient.
"In patients treated with anti-PD-1, we identified, for the first time, very efficiently, the mutations of the neo-antigen of the tumor targeted by the T cells. More importantly, we were able to identify their mutations. Cristina Puig-Saus, PhD, badociate researcher in hematology / oncology at UCLA's David Geffen School of Medicine. "We hope that a better understanding of T-cell responses that occur after blocking a point Immune control will guide the design of personalized therapies based on adoptive T cells. "
The discovery of new methods of identifying targets for immunotherapies dramatically increases the number of patients eligible for immunotherapy. The technology of IMPACT Isolation Technology® allows researchers to identify mutation-specific T cells and determine which mutations induce responses against tumors.
The lead author is Cristina Puig-Saus, PhD, badociate researcher in hematology / oncology at UCLA's David Geffen School of Medicine. The lead author is Antoni Ribas, MD, Ph.D., director of the Tumor Immunology Program at UCLA's Jonsson Comprehensive Cancer Center and professor of medicine at UCLA's David Geffen School of Medicine. Thirty-three other authors are listed in the summary.
The research was presented at the American Associate of Cancer Research's Special Conference on Immune Therapies for Cancer.
The research was funded by the Parker Institute for Cancer Immunotherapy.
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Material provided by University of California – Los Angeles Health Sciences. Note: Content can be changed for style and length.
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