The next gen of CAR-T

Atara and Moffitt announce strategic collaboration focused on multi-targeted CAR-T immunotherapies for patients with acute myelogenous leukemia and B cell malignancies

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SOUTH SAN FRANCISCO, Calif.—Atara Biotherapeutics Inc. already had a collaboration deal signed with Memorial Sloan Kettering Cancer Center around chimeric antigen receptor T cell (CAR-T) immunotherapeutic research. But recently, the company announced that it was furthering its strategy to develop next-generation CAR-T immunotherapies across multiple therapeutic areas—and leverage its off-the-shelf, allogeneic T cell immunotherapy platform—by forming a strategic collaboration with Moffitt Cancer Center as well.
In the most recent deal, the aim is to develop multitargeted CAR-T immunotherapies for patients with acute myelogenous leukemia (AML) and B cell malignancies. As part of the collaboration, Atara will gain access to novel CAR-T targeting and co-stimulation domains designed to improve T cell proliferation and enhance persistence.
“Atara is a leader in the development of off-the-shelf, allogeneic T cell immunotherapies based on their novel EBV-specific T cell technology platform,” said Dr. Marco Davila, a medical oncologist in the Department of Blood and Marrow Transplantation and medical director of the GMP Cell Production Facility at Moffitt. “I look forward to rapidly advancing our CAR-T engineering and multi-antigen targeting technologies with Atara to address the high unmet need in patients with advanced AML and B cell malignancies.”
A particular area of concern for Atara is to deal with cancers that posses diverse cell types and often become resistant to treatment, such as AML and B cell malignancies, and the Moffitt agreements seeks to work with Davila and colleagues to develop multitargeted CAR-T immunotherapies that will address that. In addition, the collaboration includes the use of novel CAR-T intracellular co-stimulatory domains based on CD28 and 4-1BB that may improve CAR-T proliferation when responding to an appropriate antigen, as well as enhance CAR-T persistence by reducing T cell exhaustion.
“Our focus is to rapidly advance development of next-generation, off-the-shelf, allogeneic CAR-T immunotherapies across multiple therapeutic areas by combining our EBV-specific T cell platform, development, manufacturing and regulatory expertise with cutting-edge T cell engineering discoveries by our external collaborators,” reported Dr. Dietmar Berger, global head of research and development of Atara. “Our new strategic collaboration with Moffitt Cancer Center builds our novel CAR-T preclinical pipeline, and has the potential to benefit patients with myeloid and B cell malignancies.”
Dr. James J. Mulé, director of the Cell-Based Immunotherapies operation at Moffitt, described Atara as “a strong technology and development partner” and noted that the company EBV-specific T cell technology platform is complementary to Moffitt’s CAR-T engineering and multi-antigen targeting technologies.
The news release about the deal was sparse on details about the terms of the agreement, mentioning nothing about financial considerations, and says only that “Atara will contribute resources and relevant experience to the research activities at Moffitt.”
In other recent news from Moffitt, the Tampa, Fla.-based facility reported that some of its researchers had examined data from more than 800 surgical patients with advanced bladder cancer. The results, published online by JAMA Oncology, show higher likelihoods of complete response or down-staging associated with a chemotherapeutic combination called ddMVAC.
“We observed a complete response rate of 41 percent for patients who received just over three cycles of ddMVAC on average,” explained Dr. Scott Gilbert, an associate member of both the Genitourinary Oncology and Health Outcomes & Behavior programs at Moffitt. “This was significantly higher than the rate of 25 percent for those who received the standard GC [combined gemcitabine and cisplatin] therapy. Patients treated with ddMVAC also had higher survival rates than those treated with other regimens, although those findings did not reach statistical significance. Larger comparative studies are needed to definitively answer questions regarding survival.”
Also, Moffitt recently participated with researchers at 28 cancer centers throughout the United States in a study to determine if the combination of ipilimumab and nivolumab is effective in untreated melanoma patients with metastatic brain disease who did not have symptoms related to the brain metastases.
Out of 94 patients who were eligible for evaluation, 54 (57.4 percent) achieved a clinical benefit in the brain for at least six months, including 24 patients with a complete response, 28 with a partial response and two with stable disease. In addition, the researchers reported that the drug combination was safe in this patient population.

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