A new CAR T-cell therapy for mesothelioma patients has Food and Drug Administration (FDA) approval to begin phase 1 clinical trials. The Atara Biotherapeutics trial uses modified CAR T-cells to improve treatment effectiveness.
The new modified therapy uses CAR T-cells engineered with two types of immunotherapy in a single treatment. Atara believes this will further improve the success of traditional CAR T-cell therapy.
How Is This CAR T-Cell Therapy Different From Traditional Therapy?
Atara Biotherapeutics is calling the CAR T-cell therapy in their trial (ATA2271) “next-generation.” The CAR T-cells used in the trial have been modified to:
- Last longer in the body.
- Contain a PD-1 checkpoint inhibitor.
What Is a PD-1 Checkpoint Inhibitor?
PD-1 checkpoint inhibitors are a form of immunotherapy. They work by blocking the PD-1 protein on a T cell. Blocking this allows the immune system (and the CAR T-cell therapy) to attack a tumor.
PD-1 checkpoint inhibitors are the second form of immunotherapy in the trial.
Previous studies found combining CAR T-cell therapy with PD-1 checkpoint inhibitors increase the success of treatment. Typically, these are two separate forms of treatment.
These two modifications amplify the treatment success of traditional CAR T-cell therapy.
How Does Traditional CAR T-Cell Therapy Work?
In traditional CAR T-cell therapy, a patient’s T cells are collected and modified to attack a specific protein. The targeted protein is found in high quantities on cancer cells. For mesothelioma patients, T cells attack mesothelin. Once the cells can pinpoint the protein, researchers multiply the cells and reintroduce them to the patient’s body.
In traditional CAR T-cell therapy, these engineered T cells may eventually disappear due to T cell death. When the T cells die without stimulating the body to make more, treatment efficacy is limited.
The first modification made to ATA2271 aims to remedy this problem. Researchers modified the T cells to last longer.
Traditional CAR T-cell therapy is often administered with PD-1 checkpoint inhibitors to increase the success of the T cells.
The second modification made to ATA2271 combines PD-1 checkpoint inhibitors with the CAR T-cells to streamline treatment.
History of the Technology Used in the Phase 1 Trial
The technology supporting the phase 1 trial has been in testing for many years. Researchers used data from mice to gain FDA approval for the phase 1 trial.
In their preclinical research, scientists examined the ATA2271 treatment protocol against an older version of CAR T-cell therapy. The older CAR T-cell therapy does not have the two modifications.
Through their testing, researchers concluded:
- ATA2271 was able to eliminate all pleural mesothelioma tumors after a single dose (19 days).
- ATA2271 engineered T cells continued to survive and function.
- ATA2271 treated mice had enhanced survival and weight gain.
- ATA2271 may prevent new tumors from forming.
The mice treated with the older form of CAR T-cell therapy had a median survival of 56 days. The median survival of the mice treated with ATA2271 was not reached. This means more than half of the mice were still alive after the preclinical trial ended.
What Could This Trial Mean for Mesothelioma Patients?
Researchers hope ATA2271 shows similar results when treating humans. As a mesothelioma treatment, ATA2271 may:
- Eradicate existing pleural mesothelioma tumors.
- Increase patient survival.
- Prevent the development of new tumors.
Without human trials, researchers cannot confirm similar results will occur.
Other CAR T-cell therapy treatments have been able to increase patient survival. Without a mesothelioma cure, experimental treatments such as immunotherapy are often used to extend patient life expectancies.
What Needs to Happen for ATA2271 to Become an Approved Drug?
The phase 1 trial approval ATA2271 received in September 2020 is one of many steps to becoming an FDA-approved drug for mesothelioma.
ATA2271 needs to pass this phase 1 trial and many other clinical trials before potentially gaining FDA drug approval.
According to an Atara spokesperson, the company is hoping to use ATA2271 to develop transformative therapies for patients with solid tumors, such as mesothelioma.
“This milestone marks an important moment in the advancement of cell and gene immunotherapy for patients, for the field and for Atara,” said Jakob Dupont, Global Head of Research and Development, Atara Biotherapeutics.