Allogene’s “Off-the-Shelf” CAR T-Cell Therapy Shows Early Promise

An “off-the-shelf” allogeneic CAR T-cell therapy, developed by Allogene Therapeutics and tested by the University of Texas MD Anderson Cancer Center, showed promising results in a Phase I trial to treat patients with metastatic clear cell renal cell carcinoma.

The advent of immunotherapy revolutionized cancer treatment. Combined gene and cell therapies such as chimeric antigen receptor (CAR) T-cell therapies, engineered to target a patient’s cancer, have proved very effective at treating some extremely sick patients.

However, the currently approved CAR T-cell therapies are autologous and require the patient’s own cells to be extracted and engineered before being reinjected into the body, a process that can take valuable time, is expensive, and needs high levels of technical expertise to prepare.

Many companies, including Allogene, are now developing allogeneic CAR T-cell therapies, which do not use a patient’s own cells, to try and make these potentially lifesaving treatments more readily accessible and affordable for patients.

The TRAVERSE study is an ongoing trial of Allogene’s CD70-targeting allogeneic CAR T-cell therapy, ALLO-316. Samer Srour, assistant professor at the University of Texas MD Anderson Cancer Center, presented Phase I results from the study today at the American Association for Cancer Research Annual Meeting in Orlando.

There is a high level of CD70 antigen expression in primary and metastatic renal cell carcinoma, but limited expression in normal tissue, which makes it a good target for a CAR T-cell therapy targeting this cancer.

In this study, 17 patients with metastatic clear cell renal cell carcinoma were treated with the experimental therapy. All the patients (82% male) had several types of prior therapy before being enrolled.

The team found that the objective response rate (any response to treatment) was 18% and the disease control rate was 82% in all the participants. In those with confirmed CD70 positive disease these two figures went up to 33% and 100%, respectively.

Safety is always a concern with CAR T-cell therapies, as while they can be very effective, potentially severe side effects such as graft versus host disease or immune effector cell-associated neurotoxicity syndrome can be a problem. Using allogeneic cells can also increase the risk of rejection by the patient’s body, although ALLO-316 incorporates additional receptor changes to reduce the risk of this happening.

In this study, 11 patients (65%) experienced cytokine release syndrome, a less severe and treatable side effect, but none had graft versus host disease or immune effector cell-associated neurotoxicity syndrome.

“As we continue to determine the appropriate dose of ALLO-316 for patients, our results demonstrate not only a manageable safety profile but also very encouraging anti-tumor activity,” Srour said, in a press statement. “In this trial, we are using an allogeneic ‘off-the-shelf’ CAR T-cell product which offers an additional benefit to our patients because we are able to get this novel treatment to our patients much faster.”

These results are promising, but historically, it has been difficult to develop CAR T-cell therapies that successfully target “solid” tumors. Solid tumors are commonly made up of a range of cells with varying genetics and finding suitable antigens to target that are not expressed elsewhere in the body is tricky. Getting the CAR T-cells into the tumors and past the potentially hostile microenvironment around them is also a challenge. Whether Allogene and others manage to overcome these potential barriers and bring their allogeneic CAR T-cell therapies to market remains to be seen.

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