On April 18, 2023, ImmVira reported preclinical study results of CAR-T enabler oHSV product MVR-7011 through poster publication at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) ("AACR") annual meeting (Press release, Immvira, APR 18, 2023, View Source;immvira-presented-preclinical-study-results-of-first-car-t-enabler-oncolytic-product-mvr-t7011-at-aacr-annual-meeting-301801147.html [SID1234630271]).
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Solid tumor has long been a challenge for CAR-T therapies. At present, most of the research efforts continue to focus on further modification of CAR-T cells, while ImmVira takes a new approach – using oHSV as vector to safely and stably deliver biomarkers that are demonstrated success in CAR-T treatment of hematologic malignancies to be precisely expressed on target tumor cell membranes for a long and continuous time window. A breakthrough advantage is that current CAR-T therapies originally targeting blood cancer can be enabled on solid tumors without any modifications required. MVR-T7011 is designed to continuously and precisely express extracellular domains of CD19 and BCMA as "biomarker" on the cell membranes of solid tumors to provide targets for CAR-T treatment, and also carry chemokine CCL5, PD-1 antibody and IL-12 genes to further enhance the killing effects on tumor cells.
At the AACR (Free AACR Whitepaper) meeting, ImmVira presented the main preclinical study results of MVR-T7011 for the first time. In the preclinical studies conducted by ImmVira, MVR-T7011 specifically deliver and continuously express CD19 and BCMA on the tumor cell surface, while these biomarkers were not detected in normal tissues, ensuring its safety for use in combination with CAR-T therapy. Similarly, the payload of CCL5, IL-12, and anti-PD-1 antibody showed a comparable expression pattern. In vitro toxicity and co-culture experiments demonstrated that MVR-T7011 did not affect the viability nor impair the proliferation of CAR-T cells and can specifically enhance their cell-killing activity on tumor cells. Results from in vivo efficacy tests demonstrated that both intratumoral (IT) and intraperitoneal (IP) administration of MVR-T7011 can activate CAR-T cell proliferation, leading to synergistic antitumor effects against various solid tumors.
ImmVira’s unique approach to modifying the tumor environment paves way for a large range of current and future emerging cancer therapies. MVR-T7011 can effectively resolve current difficulty of target heterogeneity and escape in CAR-T treatment of solid tumors through specific expression of CD19 and BCMA at the tumor site and also promote proliferation of CAR-T cells to extend treatment time window. This combination therapy is expected to help CAR-T broaden clinical application from blood to solid cancer. ImmVira has completed in-house pilot-scale manufacturing of MVR-T7011 and launched preclinical study. In the future, ImmVira will start IND filing preparation once reaching strategic partnership.