The oncolytic measles virus (MeV) vaccine strain provides a flexible vector platform which allows for targeted, tumor-restricted immunomodulation. We have developed MeV vectors to support different phases of the cancer immunity cycle. This enables therapy directly tailored to the specific immune micromilieu of individual tumors.
We have validated MeV vectors for T cell activation in preclinical models. MeV encoding bispecific T cell engagers (BiTEs) recruit cytotoxic T cells to the tumor site. Tumor antigen-specific T cell activation is achieved with MeV oncolytic vaccines. MeV encoding IL-12 directs T cell responses towards a Th1 phenotype. Combining MeV with immune checkpoint inhibition increases the ratio of effector to regulatory T cells. Furthermore, our preclinical data support the notion that MeV-mediated oncolysis can break resistance to checkpoint antibodies.
A clinical Phase Ib/II trial combining MeV with an anti-PD1 antibody in patients with metastatic pancreatic adenocarcinoma is currently in preparation. Aside from safety and anti-tumor efficacy, a main focus of the trial is the accompanying translational research program. Sequential biopsies for analysis of tumor-infiltrating immune cells, cytokine and chemokine profiling, transcriptome and immunoreceptor sequencing are performed to identify biomarkers predictive of response.
Citation Format: Christine E. Engeland, Rūta Veinalde, Christof von Kalle, Dirk Jaeger, Guy Ungerechts. Clinical translation of oncolytic measles virus for T cell activation [abstract]. In: Proceedings of the Second CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; 2016 Sept 25-28; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(11 Suppl):Abstract nr B128.
- ©2016 American Association for Cancer Research.