Abstract 5826: Development of multivalent antibody-based novel therapeutic cancer vaccine in glioblastoma multiforme (GBM) treatment

Abstract Glioblastoma multiforme (GBM) is the most prevalent high-grade malignant brain tumor and is associated with a very poor prognosis. Currently, there are no targeted therapies available for this cancer, and only general chemical drugs are being used. This is primarily due to the challenges posed by the blood-brain barrier (BBB) in drug delivery and the lack of sufficient research on its pathogenesis. Recently, a strong association between CMV (Cytomegalovirus) and GBM has been reported in various studies, and therapies targeting CMV are now undergoing clinical trials. Especially, dendritic cell (DC) cancer vaccines represent a promising therapeutic strategy for GBM, with CMV pp65 emerging as a particularly relevant target antigen. Recent clinical trials have provided evidence supporting the efficacy of select DC vaccines. Nevertheless, the production of DC vaccines remains a labor-intensive, costly, and time-consuming process, emphasizing the critical need for innovative approaches to overcome these limitations. In this study, we developed IMB-402, containing the Specific T-cell Activating Modulator (STAM) built on our engineered IgM-based multivalent antibody backbone platform, ePENDY (engineered PENtamer boDY). IMB-402 consists of ten CMV pp65-derived peptide-loaded-HLAs linked to ePENDY to stimulate priming signal of CD8+ T cell by TCR cluster. Also, we linked a CD40 agonistic scFv as a costimulatory signal molecule to the J chain of ePENDY, mimicking cognately licensed dendritic cells (DCs) to prevent T cells from entering an anergic state. We observed that IMB-402 can expand CMV pp65-specific CD8+ T cells and functionally activate these cells. Notably, we found that this effect occurs even in conditions where only CD8+ T cells are present, without any DCs. This highlights the potential of IMB-402 as an alternative to DC vaccines, offering a promising treatment option for immunosuppressive cancer patients whose DCs fail to respond appropriately. Moreover, the superior effects on expansion and activation of CMV pp65-specific CD8 T cells, compared to a competing drug currently in clinical trials, suggest that IMB-402 has the potential to become a successful treatment for GBM. Additionally, synergistic effect of IMB-402 with anti-PD1 observed using a humanized mouse model indicates that IMB-402 is expected to have robust anti-tumor activity in combination with immune checkpoint inhibitors. Overall, these findings suggest that IMB-402 could represent a new paradigm in cancer vaccine technology, highlighting its potential for development as a GBM treatment. Citation Format: Sunghyun Yoon, Sungmuk Kang, Yeji Byeon, Dongmin Chun, Hong Kyu Lee, Kyung-gi Hyun, Sunghyun Byun, Eunyoung Cho, Yongjun Kang, Chaerin Yoo, Hong Jai Lee, Chungmin Lee, Kyung-Chul Choi, Gyongsik Ha. Development of multivalent antibody-based novel therapeutic cancer vaccine in glioblastoma multiforme (GBM) treatment [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 5826.