Clinical implications of non-chromosomal neoantigens 2941

Abstract Description Shicheng Su, Jingwei Feng Breast Tumor Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, China The conventional wisdom is that neoantigens, the cardinal initiator of anti-tumor immunity, are arisen from chromosomal DNA mutations. Recent studies introduce an extra layer of complexity to the fundamental aspect of tumor neoantigens by showing that post-transcriptional and post-translational events can also generate novel peptides bound to major histocompatibility complexes. We have reported that noncanonical translation of tumor-specific circRNAs can generate cryptic peptides that serve as neoantigens and elicit efficient anti-tumor immunity(Huang et al,Nature,2024). Recently, we have initiated a phase 1 clinical trial in patients with locally advanced or metastatic Her2-CircFAM53b immunohistochemical positive breast cancer to investigate dendritic cell vaccines loaded with peptide of CircFAM53b alone or in combination with the PD-1 inhibitor (NCT06530082). In addition, our unpublished data show that DNA mutations beyond chromosomal DNA can also serve as a new source of tumor neoantigens. Topic Categories Vaccines and Immunotherapy (VAC)