Ask A Scientist:
How Can Studying Antigen-Specific T Cells Help Us Make CAR T Cells More Powerful?

ask a scientist
ask a scientistIn the last few years, CAR T cell-based immunotherapies have shown great promise in clinical trials, and scientists are continuing to advance their knowledge with hopes of developing CAR T cell therapies for a range of cancers.CAR T cells are designed to essentially function as antigen-specific T cells, which can be difficult to collect and grow outside of the body. But antigen-specific T cells can still play a vital role in helping us better understand CAR T cells and make them more powerful in fighting cancer.

The Role of Antigen-Specific T Cells in Cancer Research

Antigen-specific T cells are helping scientists better understand the T cell functions that may be vital in fighting cancer, like cytotoxic functions and tumor-killing cytokines. This, in turn, will help guide the improvement of CAR T cell therapies.The study and development of CAR T cells to recognize antigens on the membrane surface of tumor cells have received much attention, but researchers are also exploring the possibilities of natural T cell receptors (TCR) to recognize antigens on the inside of tumor cells. TCR-like CAR are being tested in vitro and in vivo with promising results.Wang et al.1 recognized the ongoing challenges in developing CAR T cell therapies, including:
  • Antigen loss relapse
  • Complications caused by on-target/off-tumor toxicity
  • Lower efficacy in solid tumors
Researchers are using antigen-specific T cells to advance CAR T cell therapies by enhancing the selectivity of CARs to make them safer for the patient by reducing off-tumor toxicity.

Antigen-Specific T Cell-Based Therapies

While there has been a strong focus on CAR T cell therapies, researchers are also having success with antigen-specific T cell therapies. Compared to CAR T cell therapies, antigen-specific T cell therapies are targeted to proteins expressed inside tumor cells, providing a wide array of potential targets while reducing the likelihood of damage to normal cells and tissues. And because they are naturally occurring cells, they do not need to be cleared out of the body after use.The Seattle Cancer Care Alliance has used T cell therapies effectively, including adoptive cell therapies for advanced melanoma and tumor-infiltrating lymphocytes, which eliminate the process of selecting individual T cells from the patient’s blood.2The Tumor Vaccine Group (TVG) in Seattle has taken a unique approach to adoptive T cell therapy by utilizing tumor-specific CD4+ Th1 cells, which have broader functionality. TVG has also linked antigen-specific Th1 with epitope spreading, which is believed to broaden the immune response and improve tumor-killing efficiency.3Adaptimmune recently began studies of their SPEAR T cell therapies in liver cancer and multiple solid tumors. Immatics has a pipeline of TCR therapies

Sources

1New development in CAR-T cell therapy. Journal of Hematology & Oncology. 20172T-Cell Therapies. Seattle Cancer Care Alliance.3Adoptive T Cell Therapy. Tumor Vaccine Group.

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