The T-cell receptor engineered T cell therapy (TCR-T) is becoming a promising treatment for cancer, with many TCR-T clinical trials being carried out for treating solid tumors. TCR-T cells engineered with a wild-type TCR, whose natural affinities are limited to ~1 to 100 μM, may not effectively target cells with downregulated tumor antigen presentation. However, affinity-improved TCRs can recognize tumor cells presenting low-density antigens.
Recent research by LI Yi's team from the Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences found that HBs-specific affinity-improved-TCR engineered T cells showed significantly enhanced potency of HCC treatment in vitro and in vivo, and also showed good safety profiles. The study was published on the J Immunother Cancer on December 17.
Treating HBV-related hepatocellular carcinoma (HCC) has been a clinical challenge. Previous investigations revealed anti-cancer efficacy of naive TCRs re-directed T cells targeting HBV-related HCC. As the expression of HBsAg in HBV-associated HCC may significantly decrease to enable tumor cells to escape immune attacks, an affinity-improved HBs-specific TCR should be a better molecule to empower T-cells to target the HCC cells. The HBs-specific Ai-TCR-T may provide a strategy to tackle the immune escape problem of HCC cells. The Ai-TCR-T cells were demonstrated to eliminate HCC tumors without recurrence in mouse xenograft models. In addition, the research has also presented an approach of harnessing TCR promiscuity to address the problem of large numbers of HBV variants hindering CTL based therapy development. Based on the epitope frequencies of HBs371-379 and HBs370-379, TCR15 could recognize more than 85% of HBV variants. This study may serve to foster an effective treatment for HBV-related HCC.
Fig. 1 Affinity-improved -T cells could eradicate HBV-related HCC in xenograft NSI mouse models. (Image by LIU Qi)
LI Yi (Corresponding author)
Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences
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LIU Qi (First author)
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In vivo therapeutic effects of affinityimproved- TCR engineered T- cells on HBV- related hepatocellular carcinoma