TCR-targeted cancer antigens, due to their high disease-specificity, have gained increased attention in recent years, especially in the treatment of solid tumors for which there has been a severe lack of “clean” targets for improved efficacy and safety profiles in clinical studies and practices.
A typical TCR structure of CD8+ T cells is illustrated as below.
In recently years, significant progress has been achieved in identifying the precise and presentable cancer antigens, some of which, excitingly, have been clinically tested for mediating immune rejection of disease cells, as briefly summarized as follows.
1. Tumor-associated antigens (TAAs): they are, generally, expressed by tumor cells but also in some healthy tissues, potentially leading to on-target off-tumor toxicity. Among them are:
2. Tumor-specific antigens (TSAs): they are genetically encoded in cancer cells but not present in the genome of any normal cells, allowing for excellent therapeutic window.
1) Viral antigens: identified in viral oncogene driven cancers; but nearly absent in normal cells.
Ebvalla developed by Atara., a first ever allogeneic (off-the-shelf) T-cell therapy approved by EU indicated for a rare but deadly lymphoma, targets presented Epstein-Barr virus (EBV) viral oncoproteins
Although not a TCR therapy, its approval clinically validates the therapeutic values of viral antigens.
More breakthroughs are expected from cancer antigen-targeted TCR therapies.
Precision makes efficacy and safety.
DetaiBio is leveraging its single T cell sorting platform and single cell RT-PCR technology to unlock its TCR discovery-based therapy research. Please contact us for potential collaboration.
1. Sun, Y., Li, F., Sonnemann, H., Jackson, K. R., Talukder, A. H., Katailiha, A. S., & Lizee, G. (2021). Evolution of CD8+ T cell receptor (TCR) engineered therapies for the treatment of cancer. Cells, 10(9), 2379.
2. Gjerstorff, M. F., Andersen, M. H., & Ditzel, H. J. (2015). Oncogenic cancer/testis antigens: prime candidates for immunotherapy. Oncotarget, 6(18), 15772.
3. Hoffmann, M. M., Brown, L., Campbell, M., Pechhold, K., Brate, A., He, X., ... & Schmitt, T. M. (2023). AFNT-211: A FAS-41BB–enhanced TCR-T cell therapy with stem-like properties targeting KRAS G12V-expressing solid tumors. Cytokine, 1, 1-50.