Abstract 4558: Immunogenicity and antitumor efficacy of live attenuatedSalmonellatyphimurium-based oral T-cell vaccines VXM01m, VXM04m and VXM06m
Authors: Sébastien Wieckowski, Lilli Podola, Marco Springer, Iris Kobl, Zina Koob, Caroline Mignard, Amine Adda Berkane, Ming Wei, Albrecht Meichle, Klaus Breiner, Matthias Schroff, Philipp Beckhove, Heinz Lubenau
Journal: Cancer Research (2017)

Abstract Significant progresses have been recently accomplished in immuno-oncology and in the development of cancer immunotherapies. However, novel solutions are necessary to overcome the peripheral tolerance and the immunosuppressive tumor microenvironment that prevent the eradication of cancer. VAXIMM is developing first-in-kind Salmonella typhi Ty21a-based oral T-cell vaccination platform for the initiation of anti-tumor cellular immune responses via a unique mode-of-action. This study summarizes the immunogenicity and preclinical anti-cancer efficacy for Salmonella typhimurium murine vaccines VXM01m, VXM04m and VXM06m which encode murine vascular endothelial growth factor receptor 2 (VEGFR2), mesothelin (MSLN) and Wilm's tumor 1 (WT1) protein antigens, respectively. Immunokinetic studies were performed in healthy animals treated with 1010 CFU/dose of either the control Salmonella typhimurium empty vector VXM0m_empty, or Salmonella typhimurium VXM01m, VXM06m or VXM04m, and antigen-specific T cells were detected with MHC class I pentamers by flow cytometry in the spleen. The anti-tumor efficacy of VXM01m and VXM04m was evaluated in the Panc02 syngeneic model of pancreatic adenocarcinoma overexpressing MSLN, and the anti-cancer activity of VXM06m was evaluated in the FBL-3 disseminated model of erythroleukemia expressing WT1, in a prime-boost setting. Treatment with each of the vaccines VXM01m, VXM04m and VXM06m induce a peak antigen-specific systemic immune response 7 to 10 days after the last vaccination. Treatment of Panc02 tumor-bearing mice with VXM01m and VXM04m single agents resulted in a significant reduction in the tumor growth rate, compared to the control group, with a median T/C of 37.6% and 19.4% respectively, 35 days after tumor challenge. Treatment of mice bearing FBL-3 leukemia with VXM06m generated a rapid and sustained anti-tumor effect with 100% (10 out of 10) of surviving animals 175 days after leukemia challenge. In contrast, treatment with VXM0_empty did not show any anti-cancer effect, with a median survival of 45 days and 0% (0 out of 10) of cancer regression. VXM01m, VXM04m and VMX06m were tolerated at the effective doses and have demonstrated consistent anti-cancer activities with substantial T cell responses in different animal tumor models. This study provides further evidence that VAXIMM’s versatile oral T-cell vaccination platform can be used to stimulate anti-tumor immunity against various tumor-associated antigens. Further studies of VAXIMM's cancer vaccine candidates, as monotherapy as well as in combination, are warranted. Citation Format: Sébastien Wieckowski, Lilli Podola, Marco Springer, Iris Kobl, Zina Koob, Caroline Mignard, Amine Adda Berkane, Ming Wei, Albrecht Meichle, Klaus Breiner, Matthias Schroff, Philipp Beckhove, Heinz Lubenau. Immunogenicity and antitumor efficacy of live attenuated Salmonella typhimurium-based oral T-cell vaccines VXM01m, VXM04m and VXM06m [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4558. doi:10.1158/1538-7445.AM2017-4558