NEW YORK – San Francisco-based Atara Biotherapeutics said on Monday that the US Food and Drug Administration has accepted its investigational new drug application for ATA2271, a mesothelin-targeting autologous CAR T-cell therapy that it is developing for the treatment of advanced mesothelioma.
The IND clearance enables Atara to begin a single-arm, Phase I trial in this indication for ATA2271, which the company developed in collaboration with Memorial Sloan Kettering.
ATA2271 is a mesothelin-directed, next-generation CAR therapy that utilizes 1XX CAR signaling and PD-1-dominant negative receptor technology to overcome checkpoint-mediated tumor suppression. Atara licensed the technology from Prasad Adusumilli at MSK, whose group designed CAR T cells with decoy PD-1 receptors that bind to PD-L1 receptors on tumor cells and keep them from being able to evade an immune system attack. Preclinical studies comparing ATA2271 against first-generation CAR treatments, showed that the engineered CAR cells in ATA2271 were less exhausted, functionally more persistent, and had better in vivo efficacy than first-generation mesothelin-directed CAR therapies.
There are currently no CAR T-cell therapies approved for solid cancers. ATA2271 targets mesothelin, an antigen that is commonly expressed on the surface of a variety of solid tumors, including mesothelioma, ovarian cancer, pancreatic cancer, and non-small cell lung cancer. According to one study, mesothelin was overexpressed in more than 70 percent of malignant mesothelioma tumors.
In addition to ATA2271, which is an autologous CAR T-cell therapy, Atara is developing an allogeneic version, ATA3271, which is also directed at mesothelin. ATA3271 is currently undergoing IND-enabling studies.