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BACKGROUND Colorectal cancer (CRC) is the third most commonly diagnosed cancer (10% of new cases in 2020) and the second leading cause of cancer-related death (9.4%) worldwide. CRC is often detected at late stages, with 38% of metastasis cases at diagnosis. This makes the development of efficient treatments crucial. Recent tremendous progress sets immunotherapy as a treatment option and opens multiple ways to address therapeutic challenges in CRC. Accordingly, we have previously developed therapeutic cancer vaccine based on stimulated tumor cells (STC) technology, that have already shown efficacy in immunocompetent mouse models. Same strategy was used in this study to generate the STC-1010 therapeutic vaccine, a novel human therapeutic CRC vaccine derivate from 3 human CRC cell lines, HCT116, HT29 and LOVO exposed to irradiation, heat shock, chemotherapy agents and haptenized. METHODS We evaluate STC-1010 for its potential to favor an immune stimulatory response on human monocytes-derived dendritic cells (moDCs) from 2 different donors through i) a derived Mixed Lymphocyte Reaction (dMLR) assay, ii) the assessment of their cytokine profile, iii) the evaluation of their capacity to activate autologous CD8+ T cells and finally iv) to promote apoptosis of three CRC cell lines (HCT116, HT29 and LS-174T). RESULTS We showed that STC-1010 induced IL-8 and IL-12 production, and reduced IL-10 during moDCs maturation. In addition, dendritic cells (DCs) exposed to STC-1010 during the maturation enhanced Interferon gamma (IFNg) production by CD8+ T cells (p=0,06 for donor 1 and p=0,0004 for donor 2) and amplified their anti-tumor activity, in combination with LPS/IFNg and CD40L. CD8+ T cells primed with STC-1010-treated DCs promote massive apoptosis of HCT116 and HT29 cells compared to the condition without STC-1010 (p CONCLUSION Taken together, our results showed that Brenus STC-1010 human vaccine is an efficient strategy to educate immune system and promote the CRC cells death in vitro lending further support in favor of STC technology based on physical or chemical stimulation and haptenization to generate human cancer therapeutic vaccine. Citation Format: Alban Bessede, George Alzeeb, Corinne Tortorelli, Jean-Philippe Guegan, Christophe Rey, Lionel Chalus, Benoit Pinteur, Paul Bravetti, Antoine Italiano. STC-1010 a new therapeutic vaccine promotes tumor cell death [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr LB224.

BACKGROUND: Colorectal cancer (CRC) is the second-most deadly cancer. Therapeutic resistance to immuno-oncology drives the need for new treatments. Stimulated tumor cell (STC) vaccine (Brenus Pharma) is composed of selected tumor cell lines, stimulated to overexpress tumor-associated or tumor-specific antigens and neoantigens including resistance factors. Haptenization of these proteins forms an immunogenic complex which stimulate the immune system to recognize and target the patient’s tumor cells expressing same resistance factors. We report in vivo results of STC-1010 vaccine, on human CRC adenocarcinoma from HT29 cell using chorioallantoic membrane (CAM) assay developed by Inovotion in immune reactive model. METHODS: This study was carried out in 2 steps: Firstly, three batches of naïve chicken embryos were stimulated by injections of STC1010 at Embryo Development Day (EDD) 11 and EDD13. At EDD18 of each batch, chicken peripheral blood mononuclear cells (PBMCs) were collected and used as anti-tumor reagent to treat respectively, at EDD 11, EDD 13 and EDD16 chicken embryos xenografted with HT29 cells. Activation of PBMCs was evaluated by IL2 and IL12 secretion quantified by ELISA. At EDD18, i.e., 9 days post-graft, in ovo anti-tumor efficacy was evaluated by tumor weight, metastatic invasion (qPCR analysis of human Alu sequence in lower CAM) and quantification of tumor-infiltrating by CD8, CD4, IFN-gamma, Perforin and TNF-alpha. RESULTS: Compared to negative control, STC-1010 vaccine induced: 1) significant increase of IL-12 and IL-2 secretion in peripheric blood during the generation of all three batches of PBMCs, confirming previous results (IL-12: +52%, p=0.0003 ; IL-2: +482%, p=0.0033); 2) a significant expression of IFN-gamma in tumor (+130,83%, p=0.0185); 3) a tendency to increase infiltrating cells: CD4+: +79,2%, CD8+: +29,4% , Perforin: +105,5%, TNFα : +78,63% confirmed by immunohistochemistry and translated into 4) a significant increase of tumor necrosis (p = 0.0267); and 5) a tendency of metastasis regression (-49%); with 6) no embryonic toxicity/mortality (daily evaluation of embryonic viability) induced by STC-1010. CONCLUSION: This in ovo study confirms efficacy of the STC-1010 observed in previous CRC syngeneic models and gives more insight about STC mechanism of action with the activation and maturation of dendritic cells, induction of CD8+ and LTh1 against tumor as the main driver of the response, all without toxicity. Inovotion’s CAM model could be used for indication screening and as a pre-proof-of-concept before syngeneic model study. Citation Format: Yan Wang, Arnaud Peyronnier, Benoit Pinteur, Lionel Chalus, Corinne Tortorelli, Paul Bravetti, Jean Viallet, François Ghiringhelli, Philippe Fornies. Inovative in vivo (in ovo) CAM model to predict efficacy and mode of action of a new antitumor vaccine stc-1010 on human colorectal adenocarcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6791.