Breaking barriers in CRC immunotherapy: Cutting-edge advances in personalized peptide vaccine development

Globally, Colorectal carcinoma (CRC) ranking second among malignancies in terms of fatality rate. Despite recent advancements in CRC immunotherapy, The therapeutic effectiveness of existing treatments remains limited attributable to the strongly immune-inhibitory milieu within CRC tumors.The development of groundbreaking therapies remains an urgent priority.As an innovative immunotherapeutic approach, antigenic peptide vaccines are increasingly studied for their potential to activate the immune system for targeted tumor cell elimination, along with advantages such as high safety and ease of production. Among these, personalized peptide vaccines (PPVs), tailored based on patient MHC-1 haplotypes and pre-vaccination immune status, have demonstrated remarkable potential in CRC treatment, particularly for microsatellite instability-high (MSI-H) subtypes.This review summarizes recent advances and key technologies in tumor peptide vaccine development, highlighting their emerging role in CRC treatment paradigms.It also examines the technological evolution from universal to individualized vaccine design. Furthermore, we delve into the influence of the immune microenvironment on vaccine efficacy and propose novel strategies for targeting immune modulation to suppress tumor metastasis.We highlight the latest preclinical and clinical findings, including advancements in novel adjuvants, neoantigen screening, nanodelivery systems, and combination therapies. Finally, we outline future research priorities and challenges in this field.