Abstract LB383: Preclinical efficacy of an innovative therapeutic cancer vaccine: A new era for immunotherapy
Authors: George Alzeeb, Iseulys Richert, Corentin Richart, Paul Marteau, Lionel Chalus, Marion Brun, Yan Wan, Corinne Tortorelli, Benoit Pinteur, Paul Bravetti, Céline Gongora, Antoine Italiano, François Ghirringhelli
Journal: Cancer Research (2025)

Abstract Colorectal cancer (CRC) is the second leading cause of cancer-related mortality worldwide. Recent advancements have established immunotherapy as a promising treatment option, opening new avenues to address the therapeutic challenges faced by CRC patients. In response, Brenus Pharma has developed a novel therapeutic cancer vaccine, leveraging Stimulated Tumor Cells (STC) technology. This innovative approach involves exposing tumor cells to physical (irradiation and heat shock) or chemical (chemotherapy) stress mimicking the CRC treatment, coupled with haptenation to enhance their immunogenicity. The anti-tumor activity of STC technology was initially validated using a murine surrogate vaccine (mSTC-1010) composed of mouse tumor cell lines. These studies demonstrated that using three distinct cell lines significantly enhanced antigenicity anti-tumoral activity compared to a single cell line. Subsequently, this approach was used for the development of the human vaccine candidate, STC-1010, which consists of six drug substances (DS) derived from three human CRC cell lines (HCT116, HT29, and Lovo). These cells were also subjected to physical or chemical stress and haptenation processes that collectively ensure the cells are no longer capable of proliferation. Transcriptomic analyses revealed the activation of stress-related pathways specific to each DS, which enabled their quantification in STC-1010 using a deconvolution strategy. The preclinical efficacy of STC-1010 was extensively evaluated. In ex-vivo studies, STC-1010 demonstrated efficacy by activating CD8+ T cells through STC-1010-treated dendritic cells, resulting in significant cancer cell apoptosis. Dendritic cells (DC) primed with STC-1010 showed an increased expression score for the antigen processing and presentation pathway compared to vehicle controls. Interestingly, CD8 + T cells activated by STC-1010-primed DC induced significant cancer cell apoptosis. In the chicken embryo Chorio-Allantoic Membrane (CAM) model, STC-1010 treatment, in combination with GM-CSF, significantly reduced tumour weight and upregulated the secretion of IL-2, IL-8, IL-12, and IFN-gamma. Furthermore, this immune-reactive model exhibited increased tumor necrosis (p = 0.0267), a 49% regression in metastases, and enhanced infiltration of CD4+ and CD8+ T cells compared to controls confirming the high potential of the STC-1010 to induce immune response in vivo. Additionally, the efficacy of mSTC-1010 was evaluated in combination with an anti-PD-1 antibody in a subcutaneous CT26 in vivo mouse model. The results showed a significant improvement in overall survival among treated mice. Based on these preclinical findings, the approval process for a clinical trial of STC-1010 was in advanced stages as of early January 2025, with regulatory authority requests nearing completion for the first-in-human study. A phase I/II trial is planned for non resectable metastatic and advanced CRC patients, comprising a dose-escalation phase I and cohort-extension phase IIa. This trial aims to evaluate the safety and preliminary effectiveness of STC-1010 in combination with immunostimulants and mFOLFOX6, with or without bevacizumab, in MSS and MSI-H CRC patients. Citation Format: George Alzeeb, Iseulys Richert, Corentin Richart, Paul Marteau, Lionel Chalus, Marion Brun, Yan Wan, Corinne Tortorelli, Benoit Pinteur, Paul Bravetti, Céline Gongora, Antoine Italiano, François Ghirringhelli. Preclinical efficacy of an innovative therapeutic cancer vaccine: A new era for immunotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_2):Abstract nr LB383.