A new variant of genetically modified immune T cell (HLA-independent T cell receptors) that can attack cancer was developed at the Memorial Sloan Kettering (MSK) Cancer Center. It was developed by genetically modifying an individual’s immune T cells and decking them up with special receptors that can detect cancer in the body. The T cells target a particular protein, or antigen present on the surface of the tumor cells. MSK’s Cell Therapy and Cell Engineering Facility collaborated with physician-scientist Michel Sadelain to create these HIT T cells. This study was published in Nature Medicine
- T-cell receptor α constant (TRAC) locus editing to create HLA-independent TCR (HIT receptor)
- HIT receptors yield greater antigen sensitivity when compared to CAR-T therapies
- Faster degranulation and cytotoxicity were facilitated by HIT T cells
- HIT T cells effectively targeted and destroyed low antigen tumors in comparison to CAR-T cells
The pitfalls of the existing CAR T-cell treatment are that some patients do not respond to the therapy and there is also the possibility of relapse. One possible reason for this is that the engineered T cells often fail to eliminate targeted cancer cells having very low levels of the antigen and this phenomenon is known as “antigen escape.”
MSK team has engineered T cells in such a way that they are highly sensitive and capable of targeting and destroying the cancer cells having low antigen levels. These redesigned cells known as HLA-independent T cell receptor (HIT) T cells increase the sensitivity of the T cells by at least tenfold and show promising results that they could be effective to target and destroy tumor cells when compared to conventional CAR-T therapies. This treatment option may help to prevent the relapse of cancer.
The different activation, sensitivity, and therapeutic thresholds of HIT T cells open new possibilities for cancer immunotherapy. HIT receptors are better suited for tumor-specific targets of low abundance. TRAC-HIT T cells can therefore be utilized to expand the domain of tumors that can be targeted by engineered T cells.
- Mansilla-Soto, J., Eyquem, J., Haubner, S., et al. (2022). HLA-independent T cell receptors for targeting tumors with low antigen density. Nature medicine, 28(2), 345–352. https://www.nature.com/articles/s41591-021-01621-1.