Clinical Study of MSH2-/- Tumor Cell Vaccines for Advanced pMMR Colorectal Cancer Patients

Summary

The goal of this clinical trial is to evaluate the safety and tolerability of an MSH2-/- tumor cell vaccine and to explore its preliminary antitumor activity and immunogenicity in adults with advanced proficient mismatch repair (pMMR) colorectal cancer who have failed, are intolerant of, or decline standard systemic therapies at West China Hospital, Sichuan University. The main objectives are to determine the incidence of dose-limiting toxicities (DLTs) and other treatment-emergent adverse events (TEAEs) related to the vaccine (n/N, %, graded per NCI CTCAE v5.0), to assess preliminary antitumor activity (objective response per RECIST v1.1, progression-free survival, and overall survival), and to characterize the vaccine's immunogenicity profile. This study using a 3+3 dose-escalation design with three dose levels of the MSH2-/- tumor cell vaccine (1×10\^7, 2.5×10\^7, and 5×10\^7 cells per dose), manufactured under GMP conditions and administered by intradermal injection. Each participant will receive four induction vaccinations (three doses every 2 weeks and a fourth dose 1 month after the third), followed by up to eight booster doses every 4 weeks based on tumor response. Participants will undergo protocol-specified safety monitoring with clinical assessments, laboratory tests, and documentation of all AEs/SAEs, and tumor response will be evaluated regularly by imaging per RECIST v1.1. After treatment completion or discontinuation, participants will enter safety and long-term follow-up for disease status and survival.

Timeline

Start

2026-06-11

Primary completion

2026-11-01

Completion

2027-10-01

Publications

• Background Pang K, Sun P, Liu X, Yang D, Zhao P, Huang Y, Cao S, Gao Y, Chen G, Yu H, Duan L, Yang Y, Zhang Z. Development of the rationale of a personalized cancer vaccine based on the in situ vaccine effect of radiotherapy: a mechanistic study of the POLARSTAR trial. Cancer Immunol Immunother. 2025 Nov 12;74(12):369. doi: 10.1007/s00262-025-04229-3.
• Background De Marco L, Micarelli E, Panula J, Nikkola J, Moilanen L, Annala M, Harkonen J, Hokkanen KE, D'Alise AM, Pylvanainen K, Peltomaki PT, Ahtiainen M, Bohm J, Mecklin JP, Scarselli E, Seppala TT. NOUS-209 Off-the-shelf Immunotherapy Has the Potential to Hit Primary and Metachronous Colorectal and Urothelial Cancers in Lynch Syndrome. Mol Cancer Ther. 2026 Apr 2;25(4):650-661. doi: 10.1158/1535-7163.MCT-25-0864.
• Background Li J, Wang P. Advances in Cancer Vaccines for Digestive System Cancers: A Systematic Analysis of Clinical Trials. Cancer Manag Res. 2025 Nov 11;17:2691-2703. doi: 10.2147/CMAR.S561298. eCollection 2025.
• Background Passardi A, Sullo FG, Bittoni A, Matteucci L, De Rosa F, Bulgarelli J, Tazzari M, Petrini M, Scarpi E, Testoni S, Miserocchi A, Tartagni O, Zani C, Iaia ML, Toma I, Viola MG, Mita MT, Tamburini E, Ridolfi L. CombiCoR-Vax trial: study protocol for a phase II, single-arm, multicenter trial of sequential pembrolizumab plus dendritic cell vaccine followed by trifluridine/tipiracil and bevacizumab in refractory microsatellite-stable metastatic colorectal cancer. BMC Cancer. 2025 Nov 22;25(1):1921. doi: 10.1186/s12885-025-15371-7.
• Background Karimzadeh F, Heidari R, Lamooki FM, Soureshjani EH, Aziz S, Mirzaei SA. Design of a multi-epitope vaccine against intestinal parasites associated with colorectal cancer using immunoinformatics approaches. Sci Rep. 2025 Dec 8;16(1):1487. doi: 10.1038/s41598-025-31713-8.
• Background D'Alise AM, Willis J, Duzagac F, Hall MJ, Cruz-Correa M, Idos GE, Thirumurthi S, Ballester V, Leoni G, Garzia I, Antonucci L, De Marco L, Micarelli E, Deng N, Secli L, Gogov S, Dong W, Jack Lee J, Bowen CM, Vornik LA, Garcia-Gonzalez A, Reyes-Uribe L, Richmond E, Umar A, Brown PH, Sinha KM, Rodriguez LM, Scarselli E, Vilar E. Nous-209 neoantigen vaccine for cancer prevention in Lynch syndrome carriers: a phase 1b/2 trial. Nat Med. 2026 Mar;32(3):1002-1011. doi: 10.1038/s41591-025-04182-9. Epub 2026 Jan 16.
• Background Huang J, Tian G. Immunotherapy in advanced colorectal cancer: Current landscape, mechanisms, challenges, and future directions. J Oncol Pharm Pract. 2026 Jan 22:10781552251414845. doi: 10.1177/10781552251414845. Online ahead of print.
• Background Hamdan F, Gandolfi S, D'Alessio F, Giannoula Y, Kolikova J, Fusciello M, Zaghen E, Napolano A, Russo S, Izci O, Bottega P, Chiaro J, Alanen KM, Antignani G, Feodoroff M, Stigzelius V, Sakalauskaite M, Sandberg J, Nieminen AI, Zambrano N, Eriksson O, Mustjoki S, Seppala TT, Gronholm M, Cerullo V. Leveraging glucan-induced trained immunity for the epigenetic and metabolic rewiring of macrophages to enhance colorectal cancer vaccine response. Nat Commun. 2026 Jan 28;17(1):1757. doi: 10.1038/s41467-026-68466-5.
• Background Yang Q, Shi X, Yang K, Gao Q, Cao Y, Huang Y, Chen L, Bao S, Xu L, Reis RL, Kundu SC, Xu H, Xiao B. A manganese-based nanoplatform leveraging chemodynamic and adjuvant effects for in situ vaccination against colorectal cancer. Biomaterials. 2026 Aug;331:124085. doi: 10.1016/j.biomaterials.2026.124085. Epub 2026 Feb 18.
• Background Wang D, Zhang H, Xiang T, Wang G. Clinical Application of Adaptive Immune Therapy in MSS Colorectal Cancer Patients. Front Immunol. 2021 Oct 13;12:762341. doi: 10.3389/fimmu.2021.762341. eCollection 2021.
• Background Keivany MR, Shojae Asrami E, Besharatloo M, Latifi H, Barjasteh AH. Advances in immunotherapy for colorectal cancer: overcoming resistance in mismatch repair-proficient tumors. Cancer Cell Int. 2026 Feb 19;26(1):151. doi: 10.1186/s12935-026-04177-7.
• Background Bolivar AM, Duzagac F, Sinha KM, Vilar E. Advances in vaccine development for cancer prevention and treatment in Lynch Syndrome. Mol Aspects Med. 2023 Oct;93:101204. doi: 10.1016/j.mam.2023.101204. Epub 2023 Jul 19.
• Background Tang TY, Colbert Maresso K, Ngeow J, Vilar E, Yap TA. Germline Mutations as Cancer Drug Targets. Cancer Discov. 2025 Nov 3;15(11):2213-2234. doi: 10.1158/2159-8290.CD-24-1241.

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