On February 27, 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 presentations highlighting next-generation CAR T platform and mesothelin-targeted CAR T clinical safety and efficacy results from Memorial Sloan Kettering Cancer Center (MSK) at the American Association of Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2019 (Press release, Atara Biotherapeutics, FEB 27, 2019, View Source [SID1234533742]). The event will be held March 29 to April 3 in Atlanta, Georgia.
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"Atara has established a leading next-generation CAR T portfolio," said Dietmar Berger, M.D., Ph.D., Global Head of Research and Development of Atara Biotherapeutics. "Encouraging pre-clinical results at AACR (Free AACR Whitepaper) show the potential of our EBV-specific T cell platform to generate off-the-shelf, allogeneic CAR T immunotherapies. We also look forward to our MSK collaborators’ clinical results of a mesothelin-targeted autologous CAR T for patients with advanced malignant pleural disease."
Mesothelin is a solid tumor-associated antigen that is expressed at high levels on the surface of cells in aggressive solid tumors including mesothelioma, triple-negative breast cancer, ovarian cancer, pancreatic cancer and non-small cell lung cancer. Initial results from an ongoing MSK investigator-sponsored Phase 1 study (NCT02414269) of a mesothelin-targeted CAR T immunotherapy for patients with malignant pleural cancers were presented at the 2018 American Society of Gene and Cell Therapy (ASGCT) (Free ASGCT Whitepaper) Annual Meeting and support activity and safety in patients with advanced mesothelioma1,2. This ongoing Phase 1 dose-escalation study continues to accrue patients and the initial results at ASGCT (Free ASGCT Whitepaper) 2018 showed enhanced response rates when patients were subsequently treated with pembrolizumab, a PD-1 checkpoint inhibitor. MSK is also investigating mesothelin-targeted CAR T cells for patients with advanced breast and lung cancer (NCT02792114).
In January 2019, Atara announced an exclusive license and collaboration agreement with MSK to develop a next-generation, mesothelin-targeted CAR T using 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 pm – 5:00 pm 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
Summary: Atara engineered EBV-specific T cells to express second-generation CD19 CARs, utilizing CD28 or 4-1BB co-stimulatory domains, resulting in high expression of both CD19 CAR and EBV T cell receptor (TCR). The chimeric EBV.CD19.CAR T cells exert potent and specific cytotoxicity against CD19-positive cells but have limited activity against CD19-negative cells. These findings establish feasibility for engineering EBV-specific T cells by leveraging next-generation CAR technologies, and support further development as an off-the-shelf, allogeneic CAR T immunotherapy platform.
Title: A Phase I clinical trial of malignant pleural disease treated with regionally delivered autologous mesothelin-targeted CAR T cells: Safety and efficacy
Session: Advances in Novel Immunotherapeutics
Clinical Trials Minisymposium Date and Time:Sunday, March 31, 2019 from 3:00 pm – 5:00 pm EDT
Location:Room A411 – Georgia World CC
Authors:Prasad S. Adusumilli, Marjorie Zauderer, Valerie Rusch, Roisin O’Cearbhaill, Amy Zhu, Daniel Ngai, Erin McGee, Navin Chintala, John Messinger, Alain Vincent, Elizabeth Halton, Claudia Diamonte, John Pineda, Shanu Modi, Steve Solomon, David R Jones, Renier Brentjens, Isabelle Riviere, Michel Sadelain
Affiliations:Memorial Sloan Kettering Cancer Center
References
1Adusumilli PS, et al. A phase I clinical trial of malignant pleural disease treated with regionally delivered autologous mesothelin-targeted CART cells: safety and efficacy – a preliminary report. Abstract 342; 2018 ASGCT (Free ASGCT Whitepaper) Annual Meeting; Chicago, IL; May 16-19, 2018.
2Adusumilli PS, et al. Regional delivery of mesothelin-targeted CAR T cell therapy generates potent and long-lasting CD4-dependent tumor immunity. Sci Transl Med. 2014 Nov 5;6(261):261ra151. doi: 10.1126/scitranslmed.3010162.