Therapeutic Cancer Vaccines in Gastrointestinal Malignancies: Advances, Challenges, and Emerging Strategies

Gastrointestinal (GI) malignancies—which comprise esophageal, gastric, colorectal, hepatobiliary, and pancreatic cancers—remain a leading global cause of oncologic morbidity and mortality. The prognosis for many patients (especially those diagnosed with advanced-stage disease) remains poor despite conventional therapies—namely, surgery, chemotherapy, and radiation. Immunotherapy, however, has emerged as a new strategy in oncology, and, in particular, the advent of cancer vaccines now provides an investigational approach to improving clinical outcomes in patients with GI malignancies. This review aims to provide a comprehensive overview of multiple vaccine-based strategies developed to better target GI cancers, spanning from early preclinical studies to the most recently completed clinical trials. We first introduce the main vaccine therapy classes and the immunologic rationale underlying each. We then summarize key findings from past and ongoing trials using a cancer-type-based approach, primarily focusing on vaccine safety and immunogenicity, and commenting on limitations in overall efficacy. Finally, we identify the challenges of applying mostly early-phase trials to clinical practice as well as future directions for integrating these vaccine-based approaches into personalized treatments for GI cancer patients.