Colorectal cancer, including MSI-high disease — a frequent target for shared-neoantigen and personalized vaccine strategies.
Nature publishes findings on neoantigen evolution and response to checkpoint inhibitor immunotherapy in colorectal cancer. Understanding how neoantigens evolve under immune pressure is vital for designing vaccines that anticipate resistance mechanisms and maintain efficacy in dynamic tumor microenvironments.
The NCI is running a Phase Ib/II trial of the Nous-209 vaccine in Lynch syndrome patients to evaluate safety, immune response, and potential effects on polyp or tumor development. The vaccine consists of man-made copies of neoantigens generated by mismatch repair errors, targeting the high-risk colorectal cancer population associated with inherited genetic variants.
Preclinical data demonstrates that cationic liposome-encapsulated CD4 and CD8 T cell neoepitopes induce superior tumor control in a murine colorectal cancer model. The liposomal formulation significantly enhanced neoepitope-specific T cell responses compared to soluble peptides, curing 60% of mice with lethal tumors.
Neoantigen-directed GRANITE immunotherapy improved progression-free survival (PFS) as maintenance therapy in microsatellite-stable metastatic colorectal cancer (MSS mCRC). This is significant as MSS mCRC has historically been resistant to immunotherapy, suggesting neoantigen vaccines may expand the addressable patient population beyond MSI-H tumors.
Biogenea Pharmaceuticals is initiating an early Phase I study of COLONYVAQ-CRC, a physics-aware, quantum-classical AI-guided personalized neoantigen vaccine for stage III MSS colorectal cancer. The trial combines the vaccine with standard chemotherapy and nivolumab, starting with a 12-patient safety cohort before potentially expanding to 50 patients.
The Affiliated Nanjing Drum Tower Hospital is recruiting for a Phase 1/2 trial of a KRAS neoantigen nanovaccine derived from engineered Lactococcus lactis bacterial membranes. The vaccine is administered as adjuvant therapy to post-operative colorectal and pancreatic cancer patients with KRAS mutations, aiming to assess safety, immunogenicity, and preliminary efficacy in preventing recurrence.
Centre Georges Francois Leclerc is initiating a Phase I study of ODI-2001, a personalized DNA neoantigen vaccine combined with a Modified Vaccinia Ankara adjuvant and ipilimumab. The trial targets metastatic or locally advanced colon and pancreatic cancers, starting with dose escalation to determine the maximum tolerated dose.