T-cell receptor recognizing circular RNA-encoded immunogenic peptide (CEIP)–HLA complexes (TCR-CEIP-HLA)

The T-cell receptor (TCR) recognizing circular RNA-encoded immunogenic peptide (CEIP)–HLA complexes is a specialized immune receptor that identifies unique antigens derived from the noncanonical translation of circular RNAs. Specifically, circular RNAs such as circFAM53B (also referred to as circCEIP) are highly expressed in certain malignancies, including breast cancer and melanoma, where they are translated into cryptic peptides rather than remaining non-coding. These peptides are presented on the cell surface by Human Leukocyte Antigen (HLA) molecules, such as HLA-A*02:01, making them visible to the adaptive immune system. TCRs that recognize these CEIP-HLA complexes mediate the activation of CD8+ cytotoxic T cells and CD4+ helper T cells, driving an effective anti-tumor response. This target is currently being explored for the development of cancer vaccines and engineered TCR-T cell therapies, as the tumor-specific nature of these circular RNAs offers a high degree of selectivity for immunotherapy.

Other names

T-cell receptor recognizing circFAM53B-encoded peptidesT-cell receptor recognizing circCEIP-encoded peptidesTCR recognizing cryptic antigenic peptides from circular RNATCR-circCEIP

Vaccination with circular RNA or its encoded peptides primes and expands antigen-specific T cells that recognize the CEIP-HLA complex on tumor cells, leading to targeted cell lysis.