On April 1, 2019 Atara Biotherapeutics, Inc. (Nasdaq: ATRA), a leading off-the-shelf, allogeneic T-cell immunotherapy company developing novel treatments for patients with cancer, autoimmune and viral diseases, reported off-the-shelf, allogeneic CAR T platform preclinical proof-of-concept results at the American Association of Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2019 in Atlanta, Georgia (Press release, Atara Biotherapeutics, APR 1, 2019, View Source [SID1234534875]).
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"Atara is building a leading next-generation CAR T pipeline," said Christopher Haqq, M.D., Ph.D., Executive Vice President and Chief Scientific Officer of Atara Biotherapeutics. "Preclinical results presented today demonstrate that our EBV-specific T cell platform has the potential to be efficiently engineered to generate off-the-shelf, allogeneic CAR T immunotherapies with favorable characteristics. We look forward to advancing this technology using novel co-stimulatory domains and intrinsic checkpoint inhibition, leveraging Atara’s research expertise and world-class T cell manufacturing capabilities."
Atara engineered EBV-specific T cells to express second-generation CD19 CARs (EBV.CD19.CAR T), utilizing CD28 or 4-1BB co-stimulatory domains, resulting in high expression of both the CD19 CAR and EBV T cell receptor (TCR). EBV.CD19.CAR T cells exerted potent and specific cytotoxicity against CD19 or EBV-positive cells and had limited activity against CD19-negative cells, while also depleting alloreactive activity. EBV.CD19.CAR T cells also demonstrated a central memory phenotype that balances expansion with effector function and is associated with persistence.
"EBV.CD19.CAR T cells exhibited optimal CAR T characteristics and in vivo function," said Blake T. Aftab, Ph.D., Vice President, Head of Preclinical and Translational Science for Atara Biotherapeutics. "These data also demonstrate that Atara’s off-the-shelf, allogeneic CAR T process effectively eliminated in vitro alloreactivity. Our findings establish feasibility for combining EBV-specific T cells with novel CAR technologies and support our further development of next-generation off-the-shelf, allogeneic CAR T clinical candidates."
EBV.CD19.CAR T anti-tumor activity was evaluated in vivo in a mouse model of aggressive lymphoma. Following a period of tumor establishment, a single injection of EBV.CD19.CAR T cells significantly inhibited tumor growth.
Additionally, yesterday at the AACR (Free AACR Whitepaper) Annual Meeting 2019, Atara’s collaborators at Memorial Sloan Kettering Cancer Center (MSK), Prasad S. Adusumilli, M.D., and Michel Sadelain, M.D., Ph.D., presented Phase 1 clinical results for a mesothelin-target CAR T immunotherapy that included safety data, anti-tumor responses, and combination data with a PD-1 checkpoint inhibitor. The results further support Atara’s planned development of a next-generation, mesothelin-targeted CAR T immunotherapy using MSK’s novel 1XX CAR signaling domain and PD-1 dominant negative receptor (DNR) checkpoint inhibition technologies for patients with mesothelin-associated solid tumors.
Abstract 2310: Functional demonstration of CD19 chimeric antigen receptor (CAR) engineered Epstein-Barr virus (EBV) specific T cells: An off-the-shelf, allogeneic CAR T-cell immunotherapy platform
Session Category: Immunology
Session Title: Adoptive Cell Therapy 2
Poster Presentation Date and Time: Monday, April 1, 2019, from 1:00 p.m. – 5:00 p.m. EDT
Location: Georgia World Congress Center, Exhibit Hall B
Authors: Blake T. Aftab, Rhine R. Shen, Christina D. Pham, Michelle Wu, Daniel J. Munson
Affiliations: Atara Biotherapeutics