Clinical Study of Novel Therapeutic Vaccine for Advanced Solid Tumors

Summary

Advanced solid tumors remain a major therapeutic challenge due to their complex heterogeneity and the immunosuppressive tumor microenvironment (TME). Although cancer vaccines are designed to induce long-lasting antitumor immunity, their efficacy is often limited by the TME's immune-evasive mechanisms. Building on this rationale, investigators developed a novel vaccine comprising irradiated tumor cells and stromal cells isolated from adjacent non-cancerous tissues or tumor tissues in combination with adjuvant. Irradiated tumor cells in vaccines such as YMN102, YMN103, YMN104, YMN105, YMN106, and YMN107 are transfected with GM-CSF; the others, such as YMN101 and YMN108, are not transfected with GM-CSF. Preclinical studies across multiple tumor models have demonstrated potent antitumor activity with no significant toxicity observed following administration. This first-in-human Phase I study is designed to evaluate the safety and tolerability of this irradiated vaccine in patients with advanced solid tumors, alongside a preliminary assessment of its antitumor activity and immunogenic profile. This is a first-in-human, Phase I, open-label study designed to evaluate the safety and tolerability of this novel vaccine. The study includes multiple arms targeting specific malignancies, including osteosarcoma, pancreatic cancer, HNSCC, colorectal cancer, HCC, glioma, and TNBC. The primary objective is to determine the incidence of dose-limiting toxicities (DLTs). Secondary objectives include assessing the objective response, progression-free survival (PFS), and overall survival (OS) per RECIST v1.1. Exploratory analyses will monitor dynamic changes in circulating biomarkers and intratumoral immune modulation to identify potential predictive markers of clinical response.

Timeline

Start

2026-06-05

Primary completion

2026-12-31

Completion

2027-06-30

Publications

• Background Song Z, Jiang Y, Zhang Y, Ao D, Ye C, Huang X, Zhou Y, Yang H, Xia R, Ai J, Wan D, Tong A, Wei Y, He X, Alu A, Wei X. Irradiated Liver Cancer Cell Vaccine Transfected With GM-CSF Induces Specific and Long-Lasting Anti-tumour Immunity Through the Synergistic Effect of Oxidised mtDNA and GM-CSF. Cell Prolif. 2026 Apr 8:e70198. doi: 10.1111/cpr.70198. Online ahead of print.
• Background Wu F, Yang J, Liu J, Wang Y, Mu J, Zeng Q, Deng S, Zhou H. Signaling pathways in cancer-associated fibroblasts and targeted therapy for cancer. Signal Transduct Target Ther. 2021 Jun 10;6(1):218. doi: 10.1038/s41392-021-00641-0.
• Background Jia H, Chen X, Zhang L, Chen M. Cancer associated fibroblasts in cancer development and therapy. J Hematol Oncol. 2025 Mar 28;18(1):36. doi: 10.1186/s13045-025-01688-0.
• Background Saw PE, Chen J, Song E. Targeting CAFs to overcome anticancer therapeutic resistance. Trends Cancer. 2022 Jul;8(7):527-555. doi: 10.1016/j.trecan.2022.03.001. Epub 2022 Mar 21.
• Background Lan T, Luo M, Wei X. Mesenchymal stem/stromal cells in cancer therapy. J Hematol Oncol. 2021 Nov 17;14(1):195. doi: 10.1186/s13045-021-01208-w.
• Background Xu M, Zhang T, Xia R, Wei Y, Wei X. Targeting the tumor stroma for cancer therapy. Mol Cancer. 2022 Nov 2;21(1):208. doi: 10.1186/s12943-022-01670-1.
• Background Senzer N, Barve M, Kuhn J, Melnyk A, Beitsch P, Lazar M, Lifshitz S, Magee M, Oh J, Mill SW, Bedell C, Higgs C, Kumar P, Yu Y, Norvell F, Phalon C, Taquet N, Rao DD, Wang Z, Jay CM, Pappen BO, Wallraven G, Brunicardi FC, Shanahan DM, Maples PB, Nemunaitis J. Phase I trial of "bi-shRNAi(furin)/GMCSF DNA/autologous tumor cell" vaccine (FANG) in advanced cancer. Mol Ther. 2012 Mar;20(3):679-86. doi: 10.1038/mt.2011.269. Epub 2011 Dec 20.
• Background Tani K, Azuma M, Nakazaki Y, Oyaizu N, Hase H, Ohata J, Takahashi K, OiwaMonna M, Hanazawa K, Wakumoto Y, Kawai K, Noguchi M, Soda Y, Kunisaki R, Watari K, Takahashi S, Machida U, Satoh N, Tojo A, Maekawa T, Eriguchi M, Tomikawa S, Tahara H, Inoue Y, Yoshikawa H, Yamada Y, Iwamoto A, Hamada H, Yamashita N, Okumura K, Kakizoe T, Akaza H, Fujime M, Clift S, Ando D, Mulligan R, Asano S. Phase I study of autologous tumor vaccines transduced with the GM-CSF gene in four patients with stage IV renal cell cancer in Japan: clinical and immunological findings. Mol Ther. 2004 Oct;10(4):799-816. doi: 10.1016/j.ymthe.2004.07.001.
• Background Zheng L, Ding D, Edil BH, Judkins C, Durham JN, Thomas DL 2nd, Bever KM, Mo G, Solt SE, Hoare JA, Bhattacharya R, Zhu Q, Osipov A, Onner B, Purtell KA, Cai H, Parkinson R, Hacker-Prietz A, Herman JM, Le DT, Azad NS, De Jesus-Acosta AMC, Blair AB, Kim V, Soares KC, Manos L, Cameron JL, Makary MA, Weiss MJ, Schulick RD, He J, Wolfgang CL, Thompson ED, Anders RA, Sugar E, Jaffee EM, Laheru DA. Vaccine-Induced Intratumoral Lymphoid Aggregates Correlate with Survival Following Treatment with a Neoadjuvant and Adjuvant Vaccine in Patients with Resectable Pancreatic Adenocarcinoma. Clin Cancer Res. 2021 Mar 1;27(5):1278-1286. doi: 10.1158/1078-0432.CCR-20-2974. Epub 2020 Dec 4.
• Background Tian H, Shi G, Wang Q, Li Y, Yang Q, Li C, Yang G, Wu M, Xie Q, Zhang S, Yang Y, Xiang R, Yu D, Wei Y, Deng H. A novel cancer vaccine with the ability to simultaneously produce anti-PD-1 antibody and GM-CSF in cancer cells and enhance Th1-biased antitumor immunity. Signal Transduct Target Ther. 2016 Nov 18;1:16025. doi: 10.1038/sigtrans.2016.25. eCollection 2016.
• Background Chen KS, Reinshagen C, Van Schaik TA, Rossignoli F, Borges P, Mendonca NC, Abdi R, Simon B, Reardon DA, Wakimoto H, Shah K. Bifunctional cancer cell-based vaccine concomitantly drives direct tumor killing and antitumor immunity. Sci Transl Med. 2023 Jan 4;15(677):eabo4778. doi: 10.1126/scitranslmed.abo4778. Epub 2023 Jan 4.
• Background Frank MJ, Khodadoust MS, Czerwinski DK, Haabeth OAW, Chu MP, Miklos DB, Advani RH, Alizadeh AA, Gupta NK, Maeda LS, Reddy SA, Laport GG, Meyer EH, Negrin RS, Rezvani AR, Weng WK, Sheehan K, Faham M, Okada A, Moore AH, Phillips DL, Wapnir IL, Brody JD, Levy R. Autologous tumor cell vaccine induces antitumor T cell immune responses in patients with mantle cell lymphoma: A phase I/II trial. J Exp Med. 2020 Sep 7;217(9):e20191712. doi: 10.1084/jem.20191712.
• Background Vermorken JB, Claessen AM, van Tinteren H, Gall HE, Ezinga R, Meijer S, Scheper RJ, Meijer CJ, Bloemena E, Ransom JH, Hanna MG Jr, Pinedo HM. Active specific immunotherapy for stage II and stage III human colon cancer: a randomised trial. Lancet. 1999 Jan 30;353(9150):345-50. doi: 10.1016/S0140-6736(98)07186-4.
• Background Nemunaitis J. GVAX (GMCSF gene modified tumor vaccine) in advanced stage non small cell lung cancer. J Control Release. 2003 Aug 28;91(1-2):225-31. doi: 10.1016/s0168-3659(03)00210-4.
• Background Mortara L, Frangione V, Castellani P, De Lerma Barbaro A, Accolla RS. Irradiated CIITA-positive mammary adenocarcinoma cells act as a potent anti-tumor-preventive vaccine by inducing tumor-specific CD4+ T cell priming and CD8+ T cell effector functions. Int Immunol. 2009 Jun;21(6):655-65. doi: 10.1093/intimm/dxp034. Epub 2009 Apr 24.
• Background Hunn MK, Farrand KJ, Broadley KW, Weinkove R, Ferguson P, Miller RJ, Field CS, Petersen T, McConnell MJ, Hermans IF. Vaccination with irradiated tumor cells pulsed with an adjuvant that stimulates NKT cells is an effective treatment for glioma. Clin Cancer Res. 2012 Dec 1;18(23):6446-59. doi: 10.1158/1078-0432.CCR-12-0704. Epub 2012 Nov 12.
• Background Liu C, Liu X, Xiang X, Pang X, Chen S, Zhang Y, Ren E, Zhang L, Liu X, Lv P, Wang X, Luo W, Xia N, Chen X, Liu G. A nanovaccine for antigen self-presentation and immunosuppression reversal as a personalized cancer immunotherapy strategy. Nat Nanotechnol. 2022 May;17(5):531-540. doi: 10.1038/s41565-022-01098-0. Epub 2022 Apr 11.
• Background Liu J, Fu M, Wang M, Wan D, Wei Y, Wei X. Cancer vaccines as promising immuno-therapeutics: platforms and current progress. J Hematol Oncol. 2022 Mar 18;15(1):28. doi: 10.1186/s13045-022-01247-x.
• Background Sellars MC, Wu CJ, Fritsch EF. Cancer vaccines: Building a bridge over troubled waters. Cell. 2022 Jul 21;185(15):2770-2788. doi: 10.1016/j.cell.2022.06.035. Epub 2022 Jul 13.
• Background GBD 2023 Cancer Collaborators. The global, regional, and national burden of cancer, 1990-2023, with forecasts to 2050: a systematic analysis for the Global Burden of Disease Study 2023. Lancet. 2025 Oct 11;406(10512):1565-1586. doi: 10.1016/S0140-6736(25)01635-6. Epub 2025 Sep 24.

Drugs

Indications