Atara Biotherapeutics announced Food and Drug Administration (FDA) approval for phase 1 of a new clinical trial. The trial (ATA2271) will focus on CAR T-cell therapy for solid tumors, including mesothelioma.
Previous uses of CAR T-cell therapy have shown success in improving patient survival. Atara refers to ATA2271 as “next-generation.” This label stems from ATA2271’s unique features, which harness two types of immunotherapy in a single treatment.
What Is Next-Generation CAR T-Cell Therapy?
Atara calls ATA2271 a next-generation therapy because of additional modifications to the CAR T-cells. The modifications amplify the performance of traditional CAR T-cells.
- First modification: Enhanced survival and function of CAR T-cells (they typically disappear over time)
- Second modification: PD-1 checkpoint inhibitor on the CAR T-cell (adds another type of immunotherapy)
CAR T-cells typically die over time without directing the body to make more immune cells. As a result, they can disappear over time. The first modification aims to enable longer-term survival of the immune cells.
Historically, other CAR T-cell therapies have been successful when combined with PD-1 checkpoint inhibitors. Until now, PD-1 checkpoint inhibitors have been administered as a separate drug.
With the second modification, ATA2271 combines CAR T-cells with inherent PD-1 inhibition. Scientists hope ATA2271 alone will achieve results similar to previous studies of CAR T-cells and separate PD-1 inhibitors.
Evidence Supporting This CAR T-Cell Treatment
The technology in this clinical trial has been in development for several years. Data used to support phase 1 comes from testing on mice.
The testing compared an older CAR T-cell therapy with the new, modified CAR T-cell therapy. Both treatments demonstrated success treating pleural mesothelioma in mice. Scientists found:
- The older therapy led to median survival of 56 days.
- The newer therapy eliminated all tumors after a single dose, in just 19 days.
The research also suggested the new therapy may help prevent new tumors from forming.
What Would This Mean for Mesothelioma Patients?
Researchers hope similar results will be seen when treating humans. After mesothelioma treatment, patients could experience tumor shrinking or eradication. They could also achieve improved survival and a lower chance of recurrence.
While there is no cure for mesothelioma, treatments such as CAR T-cell therapy may be able to improve quality of life and survival.
Researchers have not yet studied this treatment on humans. Results could vary greatly when treating humans. This clinical trial will provide more insight into the success of modified CAR T-cell therapy in mesothelioma patients.
Can CAR T-Cell Therapy Treat Other Cancers?
CAR T-cell therapies typically target a cancer-specific protein. When a CAR T-cell sees this protein, it recognizes the cell as cancerous and can attack it. ATA2271 targets a tumor-associated-protein called mesothelin.
The modified CAR T-cell therapy may be able to treat other cancers producing large amounts of mesothelin.
In addition to mesothelioma, other conditions that produce large amounts of mesothelin include:
- Breast cancer
- Ovarian cancer
- Lung cancer
- Pancreatic cancer
What Is the Current Status of the Clinical Trial?
The ATA2271 clinical trial has just advanced from the preclinical stage to phase 1 trials. It received approval for phase 1 from the FDA in September 2020.
Note: The approval is not an official drug approval. The FDA approval allows Atara to test the drug on humans. ATA2271 will have to successfully pass multiple clinical trials before full FDA drug approval may be granted.
Atara developed this treatment in collaboration with Memorial Sloan Kettering Center. Atara has several other programs in its pipeline focused on treatment for aggressive cancers and diseases.
