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Lin Wang
癌症免疫观点 ›› 2025, Vol. 1 ›› Issue (2) : 1-6.
PDF(475 KB)
PDF(475 KB)
This review aims to address the bottleneck of antigen heterogeneity that restricts the efficacy of chimeric antigen receptor (CAR) T cell therapy in solid tumors, with a focus on exploring the epigenetic regulatory mechanisms of CD70—a promising solid tumor target with aberrant overexpression—and developing next-generation CAR-T strategies to overcome CD70 expression heterogeneity. We comprehensively elucidate the epigenetic mechanisms underlying CD70 expression heterogeneity in solid tumors, and verify the core role of EZH2-mediated H3K27me3 modification in silencing CD70 in partial tumor cells and leading to ultra-low CD70 expression undetectable by conventional assays. Meanwhile, we analyze the limitations of conventional CD70-targeted CAR-T cells in solid tumor treatment, and highlight the revolutionary progress of next-generation CAR-T platforms, especially HLA-independent T cell (HIT) receptor technology, which enables the specific recognition and elimination of CD70 ultra-low expressing tumor cells. Additionally, we summarize the current status of preclinical studies and clinical trials of CD70-targeted CAR-T therapies for solid tumors, including efficacy-enhancing strategies such as epigenetic modulation, combined therapy and gene-edited allogeneic CAR-T cells. In conclusion, CD70 is a paradigm-shifting target for solid tumor immunotherapy, and the development of ultra-sensitive next-generation CAR-T platforms represented by HIT receptors has broken through the key obstacle of targeting CD70 ultra-low expressing cells. The integration of epigenetic diagnostic techniques, high-sensitivity CAR-T cells and rational combination therapy strategies will be the key to realizing the curative potential of CD70-targeted therapy, and this therapy is expected to reshape the treatment landscape of CD70-positive solid tumors, while the translation of these technological breakthroughs still faces challenges such as biomarker development, toxicity management and manufacturing scalability that need to be addressed.
CD70 / Solid tumors / Epigenetic heterogeneity / EZH2 / H3K27me3 / CAR-T cell therapy / HIT receptor / Immunotherapy / Tumor antigen escape
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