Penn Researchers Shorten CAR T-Cell Therapy Manufacturing Time

Researchers at the University of Pennsylvania Perelman School of Medicine have shortened the cell manufacturing process for CAR T-cell therapy, according to a recent release.

This process typically takes 9 to 14 days; however, a preclinical study published in Nature Biomedical Engineering details how researchers at Penn generated functional CAR T cells with enhanced anti-tumor potency in about 24 hours.

This would result in a “vast reduction in the time, materials, and labor required to generate CAR T cells”.

Traditional manufacturing approaches require T cells to be activated in a way that induces the cells to replicate and expand in number. A key to the researchers’ manufacturing approach is the lentiviral vector that delivers the CAR gene to the T cells. Lentiviral vectors are able to transfer genes like the CAR to cells without the need for this initial “activation” step, but the efficiency of this process was low.

Using engineering approaches that built in part upon knowledge of how HIV naturally infects T-cells, the researchers developed a way to overcome this requirement for T-cell activation and deliver genes directly to non-activated T-cells freshly isolated from the blood. This had a dual benefit of expediting the overall manufacturing process while also maintaining T cell potency.

“This innovative approach is remarkable in that it may be able to help patients who might otherwise not be able to benefit from CAR T-cell therapy such as those with rapidly progressing cancer due to significant time currently need to generate these therapies,” said Saba Ghassemi, PhD, a research assistant professor of Pathology and Laboratory Medicine at Penn.

“Efficient reprogramming of T cells with a CAR in as little as 24 hours in a more simplified manufacturing process without T-cell activation or extensive culture outside the body also offers the possibility of expanding where and when these therapies are produced,” Dr. Ghassemi said. “Not only might it improve the production capacity of centralized manufacturing facilities, but if simple and consistent enough, it might be possible to produce these therapies locally near the patient, which could be tantamount to addressing the many logistical challenges that impede delivery of this effective therapy especially in resource-poor environments.”