CAR T Cells: Engineering Patients’ Immune Cells to Treat Their Cancers

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Section expanding car-t cells on solid tumors


*adoptive cell transfer (ACT):

There is some skepticism that CAR T cells will have the same success in solid tumors. Dr. Rosenberg believes that finding suitable antigens to target on solid tumors—which has been a major challenge—may prove to be too difficult in most cases.

“Efforts to identify unique antigens on the surface of solid tumors have largely been unsuccessful,” he said.

Researchers estimate that the overwhelming majority of tumor antigens reside inside tumor cells, out of the reach of CARs, which can only bind to antigens on the cell surface.

As a result, as has already been shown in melanoma, Dr. Rosenberg said that he believes other forms of *ACT may be better suited for solid tumors.

But that doesn’t mean that researchers aren’t trying with CAR T cells.

For example, investigators are conducting trials of CAR T cells that target the protein mesothelin, which is overexpressed on tumor cells in some of the most deadly cancers, including pancreatic and lung cancers, and the protein EGFRvIII, which is present on nearly all tumor cells in patients with the aggressive brain cancer glioblastoma.

Early reports from these trials, however, have not reported the same success that’s been seen with blood cancers.

“As far as targeting antigens on solid tumors the same way we go after CD19, I don’t think that’s going to work in most cases,” Dr. Brentjens acknowledged.

Another key obstacle with solid tumors, he explained, is that components of the microenvironment that surrounds them conspire to blunt the immune response.

So success against solid tumors may require a “super T cell,” he said, that has been engineered to overcome the immune-suppressing environment of many advanced solid tumors. Work on a CAR T cell with these properties—an “armored” CAR T cell—is ongoing at Memorial Sloan Kettering, he said.


https://www.cancer.gov/about-cancer/tre ... ar-t-cells