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CAR T platform to treat solid tumors

Award Information
Agency: Department of Health and Human Services
Branch: National Institutes of Health
Contract: 1R43CA271880-01A1
Agency Tracking Number: R43CA271880
Amount: $368,052.00
Phase: Phase I
Program: SBIR
Solicitation Topic Code: 102
Solicitation Number: PA21-259
Solicitation Year: 2021
Award Year: 2022
Award Start Date (Proposal Award Date): 2022-08-01
Award End Date (Contract End Date): 2023-07-31
Small Business Information
Lebanon, NH 03766-1441
United States
DUNS: 828763263
HUBZone Owned: Yes
Woman Owned: No
Socially and Economically Disadvantaged: No
Principal Investigator
 (617) 320-8521
Business Contact
Phone: (617) 320-8521
Research Institution

Cancer is one of the leading causes of death worldwide. Over the years, several treatment approaches have
been developed. However, their effectiveness is severely limited by the heterogeneity of cancer cells. Thus,
there is a constant need for development of therapeutic approaches with improved outcome, such as
immunotherapy that utilizes and enhances the normal capacity of the patient's immune system. Of note, renal
cell carcinoma and ovarian cancer are considered immunogenic, or “hot” cancers, in that tumors are infiltrated
with T cells. This provides optimism that the immune system can be harnessed to be a potent and durable
weapon against these cancers.
Chimeric antigen receptor (CAR) T cell therapy has shown remarkable efficacy against hematologic tumors. Yet,
CAR T cells fail against solid tumors due to key obstacles presented by the tumor microenvironment (TME). We
propose in this application to demonstrate proof-of-concept of a novel platform that can overcome the current
barrier to CAR T cell therapy in solid tumors. Our strategy combines the specificity of anti-TIM1 CAR with
modulation of the TME by a combination of two cytokines, leading to a shift from immunosuppressive to a
cytotoxic environment. Our approach capitalizes on the recruitment and activation of a broad repertoire of
endogenous innate and adaptive immune cells, including tumor-specific T cells. Super2 and IL-33 CAR T cells
promote antitumor immunity in multiple murine solid tumor models and is impervious to antigen loss, highlighting
its potential as a universal CAR T cell platform for treatment of solid tumors. Aims will include the following: Aim
1. Design and evaluate human constructs expressing anti-TIM1 CAR, Super2 and IL-33 in vitro. Aim 2.
Demonstrate proof of concept (POC) of efficacy of a dual cytokine delivery by anti-TIM1 CAR T cells in a
humanized model of Renal cell carcinoma (RCC).

* Information listed above is at the time of submission. *

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