First-in-human trial with CAR macrophages shows promise targeting solid tumors

Preliminary findings from Penn Medicine in an ongoing first-in-human clinical trial examining the safety, tolerability and feasibility of chimeric antigen receptor macrophage (CAR M) has helped to establish the viability of this innovative immunotherapy, which advances the trailblazing scientific discovery of CAR T cell therapy—also pioneered at Penn—for solid cancer tumors and offers a promising new strategy in the fight against cancer. This preliminary data comes from a Phase 1 multicenter clinical trial, which uses a novel, gene-based cancer therapy with CAR-engineered macrophages to target recurrent or metastatic HER2-positive solid tumors.

Microscopic view of a macrophage devouring a cancer cell.

“Existing immuno-oncology treatments have offered improved outcomes for some cancer patients, yet CAR T cells, which are engineered to recognize tumor-specific antigens and are successful in some blood cancers, have not been effective in solid tumors to date,” says Saar Gill, scientific co-director of the Cell Therapy and Transplant Program at the Abramson Cancer and an associate professor of hematology-oncology in the Perelman School of Medicine. “Seeing macrophages show high CAR expression, viability, and purity, successfully manufactured from cancer patients and are well tolerated, has us excited to be conducting this trial to help us understand the impact CAR M cells have on targeting solid tumors.”

CAR M is an individualized therapy that begins with isolation of primary monocytes from blood drawn from a patient, which are then modified with the desired antigen-specific chimeric receptor—for example, anti-HER2. The resulting CAR M modified cells are cryopreserved and will be infused back into the patient. CAR M may be able to reach immunologically “cold” tumors, or those that are typically undetectable or unresponsive to the immune system, to help activate them to be more receptive to treatment.

This story is by Caren Begun. Read more at Penn Medicine News.