New technology enables more personalized treatments for advanced cancer patients

Results

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). Use of ultra-sensitive and high-speed isolation technology (called imPACT insulation technology)^®) designed to isolate neoepitope-specific T cells, UCLA researchers were able to characterize and identify the neo-antigens responsible for antitumor responses in a patient treated with anti-PD-1 blockade and to isolate T cell receptors responsible for this effect.

Context

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.

Method

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, high-throughput mutations of tumor neo-antigen targeted by T cells. More importantly, we were able to identify their cell receptors. T and demonstrate that they can actually specifically kill tumor cells. We hope that a better understanding of T-cell responses after blocking an immune control point will guide the design of personalized therapies by adoptive T cells. "

Lead author Cristina Puig-Saus, PhD, Associate Researcher in Hematology / Oncology at David Geffen Medical School, UCLA

Impact

The discovery of new methods of identifying targets for immunotherapies dramatically increases the number of patients eligible for immunotherapy. ImPACT insulation technology^® allows researchers to identify mutation-specific T cells and understand which mutations induce responses against tumors.