COLONYVAQ™, a Quantum-Classical Guided Personalized Neoantigen Vaccine for MSS Stage III Colorectal Cancer

Colorectal cancer is a leading cause of cancer-related mortality. In stage III disease, recurrence remains frequent despite curative-intent surgery and adjuvant oxaliplatin-based chemotherapy. Immune checkpoint inhibitors have transformed outcomes in mismatch repair-deficient / microsatellite instability-high colorectal cancer, but microsatellite-stable / pMMR tumors typically exhibit a lower tumor mutational burden and a poorly inflamed, immunosuppressive microenvironment. As a result, conventional PD-1 blockade alone provides minimal benefit in MSS/pMMR disease. Earlier vaccine approaches in colorectal cancer focused on tumor-associated antigens such as CEA, MUC1, survivin, MAGE and multi-TAA peptide cocktails. These studies showed that peptide and dendritic-cell-based vaccines can induce antigen-specific T-cell and B-cell responses, yet objective responses were rare, clinical benefit was modest, and off-tumor toxicities were a concern because TAAs are frequently expressed in normal tissues. Tumor-specific neoantigens, generated by non-synonymous somatic mutations, are in contrast restricted to malignant cells, escape central tolerance, can elicit higher-avidity T-cell responses, and minimize off-tumor toxicity. Early colorectal and pan-cancer neoantigen trials, as well as shared-neoantigen programs such as SLATE-KRAS and fully personalized viral-RNA platforms such as GRANITE, have demonstrated that multi-neoantigen vaccination is feasible, safe, and immunogenic, particularly in low-burden or maintenance settings and when combined with checkpoint blockade. The adjuvant neoantigen dendritic cell vaccine plus nivolumab trial in resected hepatocellular carcinoma and colorectal liver metastases further supports the idea that personalized neoantigen vaccination in the minimal residual disease (MRD) setting can augment neoantigen-specific T-cell responses and potentially improve relapse-free survival. Oxaliplatin-based regimens (mFOLFOX6 or CAPOX) can induce immunogenic cell death, exposing calreticulin and other danger signals that enhance dendritic cell uptake and cross-presentation of tumor antigens. Nivolumab, by blocking PD-1, relieves inhibitory signaling on activated T cells. Combining a personalized multi-neoantigen peptide vaccine with immunogenic chemotherapy and PD-1 blockade is therefore expected to increase antigen release, improve antigen presentation, and augment effector function, potentially converting immunologically "cold" MSS tumors into more inflamed, "hot" lesions amenable to durable immune surveillance in the adjuvant setting.

COLONYVAQ-CRC: Quantum-Classical, Physics-Aware Neoantigen Prioritization Most existing neoantigen pipelines treat epitope ranking as mainly statistical. COLONYVAQ-CRC introduces a physics-aware, quantum-classical AI layer, adapted from Tamavaq, to generate an auditable, mechanistic chain from sequencing to clinical peptide selection. For each candidate peptide-HLA pair p, the system constructs a unified feature representation Φ(p), which concatenates sequence-based, biological, quantum, structural, and energetic evidence: Φ(p)=\[e\_"CNN" (p),"" aux(p),"" z\_Q (p),"" ϕ\_"struct" (p),""ϕ\_"dock" (p)\]. The term e\_"CNN" (p) denotes a deep sequence/HLA embedding derived from convolutional or transformer models trained on large immunopeptidome datasets. The auxiliary block aux(p) compiles antigen processing and expression priors such as proteasomal cleavage likelihood, TAP transport propensity, transcript abundance, clonality and, when available, ctDNA/MRD information to approximate the effective antigen source strength. The quantum descriptor z\_Q (p) is a low-dimensional classical vector that parameterizes a quantum circuit embedding. The structural term ϕ\_"struct" (p) summarizes pocket occupancy and residue-residue contacts in modeled peptide-HLA complexes. Finally, ϕ\_"dock" (p) aggregates docking ensemble statistics including pose energies, dispersion and conformational diversity.