New CAR-T model for solid tumors

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New research from the University of Pennsylvania (UPenn), who are allied with Novartis, suggests new potential for CAR-T cell therapies in treating solid tumors.

CAR-T cell therapies have already demonstrated great promise in treating cancers but have been mostly limited to blood cancers. In hopes of overcoming this, academic researchers and leading companies in the field are working to develop second generation strategies. Assistant professor of medicine at UPenn, Dr Edmund Moon, who is allied with Novartis, has completed a preclinical study that could help expand the potential of CAR-T therapies to solid tumors.

Dr Moon’s research primarily focused on the checkpoint inhibitory receptor, PD-1, which is targeted by two approved therapeutics, pembrolizumab and nivolumab. These have been shown to have limited efficacy due to a low count of “tumor-reactive immune cells” which are essential in attacking the cancer.

The UPenn researchers developed a next-generation immune cell by inserting an engineered switch receptor into the CAR-T cells via a viral vector. These new CAR-T cells were able to target three key proteins on the cancer cells. Additionally engineering these cells with part of the PD-1 receptor enabled it to recognize its tumor counterpart, PD-L1, and with a portion of CD28 engineered as the cell-signalling component of the receptor, allows it to signal an immune response.

Comparing the switch receptor CAR-T with the original CAR-T demonstrated a significant improvement in performance in mice.

“We are hopeful that the great success seen with investigational CAR T-cell therapy in blood tumors will occur in solid tumors as well, as we continue to study ways to combine other immunotherapies with T-cell therapy, and better understand ways to augment T-cell function in solid tumors,” explained Dr Moon.

Source: Modified CAR T Cells May Overcome Immune Suppression and be Effective Against Solid Tumors in Preclinical Models; Press Release