Research in the laboratory of Carl DeSelm, MD, PhD, is focused on developing novel CAR immune therapies for solid tumors.
Ultimately the success of CAR T cells for solid tumors will require overcoming multiple hurdles. One major difficulty is identifying target molecules that are only expressed on the tumor cells, and not on critical normal tissues. Further, if not every tumor cell expresses the target molecule, the cancer will not be cured, as the negative cells that escape will eventually grow back. Beyond this there are additional barriers, including poor penetration of the tumor by CAR T cells, a locally immunosuppressive microenvironment, and inherent resistance of many tumors to T cell killing.
Though these obstacles are daunting, in some circumstances, such as certain checkpoint inhibitor or CAR T cell patients, T cells can overcome all of these barriers and eliminate bulky, disseminated cancer with lasting response and few side effects. The mechanisms by which this occurs in some patients and not others, and how to achieve it more reliably, is actively being investigated in the DeSelm laboratory.
The DeSelm Lab currently is working on CAR T-cells that locally secrete additional immune modulators upon tumor binding for targets on a variety of solid tumors, including brain, breast, prostate, pancreas, lung, and bladder cancer. These studies are currently being performed in animals, but we hope to translate the most effective of these CAR therapies to patients.
A second major focus in the laboratory is developing CARs for other immune cells, such as macrophages. Macrophages naturally infiltrate tumors and can kill by a different mechanism, particularly by “eating” the tumor cells. Further, macrophages can stimulate tumor killing by activating tumor-reactive T cells. We are developing CARs that stimulate tumor phagocytosis and antigen presentation to identify novel and potentially more effective ways to eliminate aggressive and resistant cancers with cellular therapy.