Using CAR T to fight solid tumors

T cells that have been genetically altered to express chimeric antigen receptors (CARs) have demonstrated cancer-fighting activity against hematologic cancers. However, CAR T cell therapy’s potential to treat solid tumors remains a question because of the lack of cell surface antigens specific to cancer cells. A recent study published in the journal Immunity has shown that, in fact, CAR T holds promise for a wide range of malignancies.

The rush to find a cure

The finding, published by lead author Avery Posey, was the result of the research team trying to find a treatment for their colleague and friend diagnosed with end-stage cancer. The patient’s tumor did not possess any of the markers found on the cancers that Posey and co-authors Laura Johnson and Carl June focused on in their laboratory at the Perelman School of Medicine at the University of Pennsylvania.

Instead, the researchers found a protein glycosylation modification on the mucin 1 (MUC1) protein on the patient’s tumor, which turned out to be present on several different types of tumors. This Tn glycan on the MUC1 protein is absent on normal cells.

Scanning electron micrograph of a healthy human T cell. Credit: NIAID

A collaboration is borne

In order to test a CAR T therapy for this marker, the team collaborated with other researchers at the University of Copenhagen and the University of Chicago. They developed an antibody called 5E5 to recognize the Tn glycan on the MUC1 protein which targeted cells of a variety of cancers, including ovarian, breast, leukemia and pancreatic cancer, but did not recognize normal cells. The group created CAR T cells expressing the antibody and tested them in mice with pancreatic cancer to represent solid tumors and leukemia as a representative blood cancer. All six mice with pancreatic cancer treated with the anti-Tn-MUC1 CAR T cells were still alive after the 113-day study period, whereas two-thirds of the non-Tn-MUC1 CAR T cell-treated mice did not survive.

More work to be done

According to Dr. Posey, “This is the first approach using a patient’s own immune cells that can specifically target this class of cancer-specific glycoantigens, and this has the great advantage of applicability to a broad range of cancers.” While these findings have great potential to treat a variety of cancers, much more work is needed. CAR T is still in its infancy as a treatment with a number of clinical trials ongoing for blood cancers. Unfortunately, the investigators’ colleague lost her battle with cancer before the treatment could be trialed in the clinic. Certainly, the hope is that CAR T for solid tumors becomes a successful treatment to help others as soon as possible.

MUC research

The MUC family of proteins are expressed on the apical surface of epithelial cells that line the mucosal surfaces of many different tissues, including lung, breast, stomach and pancreas. At Kerafast, we offer several MUC1 antibodies, including some from Donald Kufe, MD, and a MC-38 MUC1 cell line from Drs. Schlom and Hodge at the National Cancer Institute.