This paper describe a breakthrough in cancer immunotherapy addressing why CAR T cells often fail to eliminate solid tumors. Research reveals that many tumors appearing to be CD70-negative actually possess ultralow levels of the antigen that are hidden by epigenetic silencing via the protein EZH2. To overcome this, scientists engineered a more sensitive HLA-independent T cell (HIT) receptor capable of detecting these trace amounts of CD70. When combined with specific costimulatory ligands, these HIT T cells successfully achieved complete tumor eradication in models of kidney, ovarian, and pancreatic cancer. This discovery suggests that CD70 is a universal target across many malignancies if treated with high-sensitivity receptors. Ultimately, the study demonstrates that antigen heterogeneity is often a matter of detection limits rather than a total absence of the target.

References:

• Hanina S A, Park T, Lopez M, et al. Sensitive CAR T cells redefine targetable CD70 expression in solid tumors[J]. Science, 2026, 391(6788): 896-905.