The U.S. Food and Drug Administration (FDA) has given a green signal to Atara Biotherapeutics to jump from preclinical studies to phase I clinical trials of CAR T-cell therapy. The company has termed this improved CAR T-cell therapy clinical trial as “ATA2271”. ATA2271 will test the efficacy of CAR T-cell therapy for the treatment of solid tumors, including mesothelioma cancer.

FDA accepted the IND (Investigational New Drug) application for the phase 1 clinical study of ATA2271 at the 2020 American Association for Cancer Research (AACR) Virtual Annual Meeting II. Atara Biotherapeutics announced the FDA’s approval on September 8th, 2020.

“We are pleased the FDA has cleared the IND for ATA2271 for the treatment of advanced mesothelioma. This milestone marks an important moment in the advancement of cell and gene immunotherapy for patients, for the field, and for Atara.” Jakob Dupont, MD, Global Head of Research and Development at Atara Biotherapeutics stated in the press release. “This milestone marks an important moment in the advancement of cell and gene immunotherapy for patients, for the field and for Atara,”

Next-generation CAR T-cell therapy

ATA2271 is a next-generation CAR T-cell therapy simply because of the modifications introduced to the CAR T-cells. These modifications improve the functionality and efficiency of the CAR T-cells. These modifications include:

Enhancement in the survival time of the CAR T-cells, which will simultaneously enhance their performance.
Normally, CAR T-cells disappear/ die without signaling for the production of more T-cells. This modification helps in improving the life of CAR T-cells in the body.

This first modification was researched and developed at the lab of Michel Sadelain, MD, Ph.D. He is director of the Center for Cell Engineering at Memorial Sloan Kettering.

Genetic modification of the CAR t-cells by the addition of PD-1 checkpoint inhibitors on them, thus improving the efficiency of these cells.

The combination of CAR T-cell immunotherapy and PD-1 checkpoint inhibitors has proved incredibly efficient and has emerged as a successful immunotherapy.

Administration of only PD-1 checkpoint inhibitors also has positive results. This second modification combines the CAR T-cells with PD-1 inhibitors.

The technology of this second modification was developed under the supervision of Prasad S. Adusumilli, MD, FACS. Dr. Adusumilli is a thoracic surgeon and is co-director of the mesothelioma program at Memorial Sloan Kettering.

Jakob Dupont has stated, “As the first-ever CAR T therapy leveraging the combination of PD-1 DNR checkpoint inhibition and 1XX CAR signaling technologies to enter the clinic, we are advancing a unique CAR T program with the goal of developing transformative therapies for patients with solid tumors.”

What does it mean for Mesothelioma patients?

The FDA approval for the clinical trial phase 1 surely lightens up a beacon of hope for mesothelioma patients all around the world. The modified CAR T-cell immunotherapy has shown quite encouraging results in preclinical trials. Researchers are hopeful for seeing similar results of this treatment on humans as well.

This means that patients may experience shrinkage or eradication of tumors; and improved survival time after this treatment.

With no sure cure for mesothelioma cancer, this improved CAR T-cell therapy may improve the survival time and quality of life of mesothelioma patients.

Current status of the ATA2271 clinical trial

Atara Biotherapeutics received approval for phase I of the ATA2271 clinical trials from the FDA in September 2020. After this approval, the company has jumped from the preclinical stage to phase I clinical trials recently.

Although it is a great development, it is important to note that the FDA has not officially approved this treatment for mesothelioma patients. Rather, the FDA has allowed Atara to test the ATA2271 on humans. This immunotherapy has to pass several successful clinical trials to get final full FDA approval. And then it shall be used for the treatment of malignant pleural mesothelioma patients. To get an overview of the whole project and the succession of this clinical trial, check out the Atara Bio Pipeline.