25 January 2022 | Tuesday | News
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Solid tumor has long been a challenge for CAR-T. Major obstacles include solid tumor heterogeneity, lack of tumor associated antigens as CAR-T targets, complicated tumor microenvironment ("TME"), inadequacy of T-cell homing to the tumor site, T-cell immunosuppression and exhaustion and etc. While most efforts continue to focus on further modification of CAR-T cells, including locating highly-specific targets, receptor modification, recognition of multiple antigens, modulating CAR-T viability through other drugs, incorporation of external "weapons" to overcome immunosuppression and etc. ImmVira takes a new approach, leveraging viral vectors that can modify the tumor into targets to achieve a more direct and safe effect.
The first three products of MVR-T7 series are MVR-T7011 with the combination of CD19 and BCMA, MVR-T7012 with the combination of CD19 and Trop-2, and MVR-T7013 with the combination of CD19 and HER-2. With MVR-T7, extracellular domains of aforementioned biomarkers can be continuously and precisely expressed on the cell membranes of solid tumors after customized oHSV entering into tumor site, providing targets for CAR-T treatment. At the same time, MVR-T7 series also carry chemokine CCL5, PD-1 antibody and IL-12 genes to further enhance the killing effects on tumor cells.
The design principle of MVR-T7 series is to use oHSV as vector to safely deliver biomarkers that have demonstrated success in CAR-T treatment of hematologic malignancies and make these biomarkers viable in solid tumors. Specifically engineered to allow biomarkers to be precisely expressed on target tumor cell membranes with a long and continuous time window, CAR-T therapy can be enabled on solid tumors without any further modification on the CAR-T cells targeting blood cancer. In addition, oncolysis caused by oHSV turn dense solid tumor tissues soft and loose, allowing CAR-T penetration into solid tumor stroma. More importantly, incorporation of CCL5 carried by the product enhances T-cell infiltration in solid tumors. CCL5 attracts and activates T-cells, and also promote macrophages and dendritic cells to secret CXCL9 thus further promoting circulating T-cell infiltration. Besides tumor modification, exogenous therapeutic genes including PD-1 antibody and IL-12 can induce prompt IFN-γ secretion to create 3-in-1 anti-tumor effects. The elegant design is a breakthrough to achieve maximum treatment benefit for CAR-T therapy on solid tumors.
As CAR-T enabler, MVR-T7 series made optimal modification of viral vector, combinations of biomarkers, chemokines and promoters based on scientific and treatment target specific design, in accordance with scientific foresight and clinical application. Completing rigorous in-vitro and in-vivo experiments, these three products did not compromise proliferation and viability of CAR-T and showed significant anti-tumor activities used in combination with CAR-T. Currently, ImmVira has independently completed in-house pilot-scale manufacturing for MVR-T7011, the first product of MVR-T7 series, and comprehensively launched extensive research for the purpose of IND application with strategic partners. In recent years, several CAR-T products have been approved as treatment, this breakthrough to treat solid tumors will open a significant market opportunity for CAR-T therapy.
ImmVira's unique approach to modify the tumor environment paves way for a large range of current and emerging cancer therapies to become more effective. In addition to CAR-T, MVR-T7 series is designed to enhance treatment outcome when in combination with CAR-NK, ADC and BiTE. ImmVira will continue to adhere to a science-driven, original innovations and patient-focused philosophy, to continue research and development of new viral vectors drugs. Meanwhile, non-viral vector anti-tumor pipelines research, such as engineering exosomes for targeted drug delivery are underway with innovations in specific delivery scenarios or safety parameters to reignite the hope for patients around the world.