SEP 01, 2022 3:00 AM PDT

Pre-clinical Study Describes a Strategy to Improve Adoptive Cell Therapy

WRITTEN BY: Katie Kokolus

Immune cells, known as T cells (also called T lymphocytes), play a vital role in the anti-tumor immune response.  T cells find, attack, and, when effective, kill cancer cells.  Adoptive cell transfer (ACT), also called adoptive cell therapy, describes a form of cancer immunotherapy carried out by administering T cells to patients, providing them with an arsenal of killer cells. 

T cells use a protein present on their surface called a T cell receptor (TCR) to identify cancer cells.  Cancer cells express a protein on their surface called an antigen , and when a TCR binds an antigen, the T cell becomes activated to kill the cancer cell.  An integral part of this system is regulated because each TCR recognizes a specific antigen.  Immunity is most robust if a patient has a high number of T cells possessing TCRs programmed to find the antigen on their cancer.  

In some situations, doctors can evaluate the specific antigen present on a patient’s cancer cells.  In such a case, it may be possible to capitalize on the TCR’s role in activating the anti-tumor immune response by administering the patient T cells engineered to express antigen-specific TCRs.  This method of ACT utilizing specially engineered TCRs has some efficacy as a cancer therapy, particularly in some types of melanoma.  Unfortunately, immunosuppressive factors in the tumor microenvironment (TME) can limit the effectiveness of engineered T cells.

A recent study in Science Immunology provides new evidence on overcoming an immunosuppressive TME that allows ACT to work more effectively.  This work focuses on a highly specialized subset of NKT cells, immune cells which perform functions of both T cells and natural killer (NK) cells.  The cells utilized in this study, called invariant NK T (iNKT) cells, limit the functions of suppressive cells in the TME. 

The researchers engineered iNKT cells to express a specialized TCR.  When transferred into mice, the TCR-engineered iNKT cells proved more effective in controlling tumors than unmodified iNKT cells or T cells engineered with the same TCR. The study found that the TCR-engineered iNKT cells both killed cancer cells and reduced the activities of the immunosuppressive cells in the TME.   The authors then utilized a multistage vector platform which ensured delivery of the transferred cells to the tumor.  This drug delivery enhancement, combined with an iNKT agonist, improved both anti-tumor functions. 

The authors conclude that harnessing the dual functions of iNKT cells to attack cancer cells and simultaneously hinder immunosuppressive cells could become a novel ACT strategy.

 

Sources: Nature, Science Immunology

About the Author
PhD
PhD in Tumor Immunology. I am interested in developing novel strategies to improve the efficacy of immunotherapies used to extend cancer survivorship.
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