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AI / Methods
Identification of immunogenic neoantigens from intron retention in colorectal cancer - Nature
Identification of immunogenic neoantigens from intron retention in colorectal cancer Nature
Colorectal cancer, including MSI-high disease — a frequent target for shared-neoantigen and personalized vaccine strategies.
Identification of immunogenic neoantigens from intron retention in colorectal cancer Nature
A study from Vietnam National University developed a colorectal cancer-specific off-the-shelf neoantigen panel targeting shared mutations. By integrating TCGA mutation data with HLA class I binding predictions across 68 alleles, the team identified candidates with broad coverage for both Asian and Caucasian populations to address limitations in population-specific utility.
Researchers tested genetically modified outer membrane vesicles (OMVs) carrying poly-neoepitopes in a mouse model of colorectal cancer with lung metastasis. The approach aims to enhance immunotherapy efficacy by leveraging OMVs as a delivery platform for neoantigens, offering a potential preclinical proof-of-concept for targeted vaccine strategies.
The National Cancer Centre, Singapore is recruiting for a Phase II study of a neoantigen dendritic cell vaccine in hepatocellular carcinoma and liver metastases from colorectal cancer. The single-arm trial combines the adjuvant intra-dermal vaccine with intravenous nivolumab.
Dr. Haldar discusses future directions for NeoAg-VAX in colorectal cancer, signaling ongoing industry interest in this platform's application within the MSS mCRC population.
Biogenea Pharmaceuticals is recruiting for an early Phase I trial of COLONYVAQ-CRC, a physics-aware, quantum-classical AI-guided personalized neoantigen peptide vaccine. The study evaluates safety and tolerability when administered with standard adjuvant oxaliplatin-based chemotherapy and nivolumab in patients with completely resected stage III microsatellite-stable (MSS) colorectal cancer.
Providence Health & Services is managing an intermediate-size expanded access program for T-cells engineered with TCRs targeting the KRAS-G12D neoantigen in advanced pancreatic and colorectal cancers. The protocol involves autologous T-cell transduction with GMP-grade retroviral vectors followed by lymphodepletion, offering a potential treatment avenue for patients with limited options harboring this specific mutation.
Centre Georges Francois Leclerc is planning a Phase 1 study for ODI-2001, a personalized DNA neoantigen vaccine combined with an MVA viral adjuvant and ipilimumab. The trial targets metastatic or locally advanced colorectal and pancreatic cancers, beginning with dose escalation to determine the maximum tolerated dose before expanding to assess progression-free survival.
The Affiliated Nanjing Drum Tower Hospital is conducting a phase 1/2 trial of a KRAS neoantigen nanovaccine derived from engineered Lactococcus lactis bacterial membranes. This adjuvant therapy targets post-operative colorectal and pancreatic cancer patients with KRAS mutations to assess safety, immunogenicity, and preliminary efficacy.
Ying Yuan is recruiting for a phase 1 trial of iNeo-Vac-T01, a personalized T-cell therapy based on tumor neoantigens, in advanced colorectal cancer. The study aims to evaluate the feasibility, safety, and efficacy of this individualized therapeutic strategy.
Ying Yuan has completed a phase 1 study evaluating neoantigen-based personalized immunotherapy as consolidation therapy after standard adjuvant treatment in resectable stage III colorectal cancer and NSCLC. The trial confirmed that the 300 μg/peptide dose is well-tolerated, establishing safety for future efficacy assessments.
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.