Adoptive cell transfer (ACT) is a promising cancer immunotherapy that involves isolating T cells from cancer patients that are capable of targeting their tumor, selecting the more active T cells and expanding those in the lab, and then transfusing them back into patients.

The ACT is already available in the clinic for some diseases—CAR-T therapy, a form of the ACT, was approved by the FDA in 2017 for children with acute lymphoblastic leukemia and adults with advanced lymphomas—and many clinical trials of another form of the ACT are underway in melanoma.

Although ACT has produced dramatic results in some of these patients, not all respond, and the therapy has thus far proven less effective against solid tumors. The optimizing ACT could enable more patients with more types of cancer to benefit from the promising treatment.

CAR-T therapy

Combining ACT with a pan-PIM kinase inhibitor and a PD1 inhibitor improves outcomes in a preclinical model, report researchers at the Medical University of South Carolina (MUSC) in an article published online in October by Clinical Cancer Research.

They showed that this triple combination treatment (PPiT) doubled the migration of anti-tumor T cells to the tumor site and quadrupled survival in mice compared to ACT alone.

"With this triple combination therapy, many more T cells persisted. That's important for ACT, because the longer the transfused T cells say inside the host to fight tumor cells, the better," said Shikhar Mehrotra, Ph.D., senior author of the article, who is co-scientific director of the oncology and immunotherapy programs in the Department of Surgery at the Medical University of South Carolina and a member of the Hollings Cancer Center.

Of the two agents administered along with ACT as part of this triple combination therapy, PD1 inhibitors are far better known. PD1 and PDL1 inhibitors take the brakes off of the immune system, enabling its T cells "to see" tumors that had been hiding in plain sight.

Clinical successes with checkpoint inhibitors, including PD1 and PDL1inhibitors, ushered in immunotherapy as the fifth pillar of cancer therapy, where it joined the ranks of chemotherapy, surgery, radiotherapy and targeted therapy.

In contrast, PIM kinase inhibitors are relatively new kids on the block. PIM kinases are proteins that can control many cellular processes, including energy. A clinical roadblock for the ACT has been the lack of energy shown by readministered T cells. Mehrotra and his team set out to find whether targeting PIM kinase with an inhibitor could help these readministered cells maintain their energy longer.