Avidity optimization of a MAGE-A1-specific TCR with somatic hypermutation.

ABSTRACT: A T-cell receptor (TCR) with optimal avidity to a tumor antigen can be used to redirect T cells to eradicate cancer cells via adoptive cell transfer. Cancer testis antigens (CTAs) are attractive targets because they are expressed in the testis, which is immune-privileged, and in the tumor. However, CTAs are self-antigens and natural TCRs to CTAs have low affinity/avidity due to central tolerance. We previously described a method of directed evolution of TCR avidity using somatic hypermutation. In this study, we made several improvements to this method and enhanced the avidity of the hT27 TCR, which is specific for the cancer testis antigen HLA-A2-MAGE-A1_278-286 . We identified eight point mutations with varying degrees of improved avidity. Human T cells transduced with TCRs cont

SUBMITTER: Bassan D 

PROVIDER: S-EPMC8252751 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature