Boosting tumor-infiltrating lymphocyte therapy with the power of B cells

Researchers at Moffitt Cancer Center have found that tapping into the body's own immune system and activating a type of immune cell known as B cells, could be the key to boosting the effectiveness of tumor-infiltrating lymphocyte, or TIL therapy. Results of their study were published in the Journal for Immunotherapy of Cancer.

TIL therapy starts with doctor's removing tumors from the patient. These tumors are sent to a lab, where they are dissected to collect immune cells that have infiltrated the tumor, known as tumor-infiltrating lymphocytes (TILs). These TILs are then grown in large quantities and reinfused into the patient's body to seek out and attack cancer cells. While it's already FDA-approved for melanoma, new Moffitt research shows that a simple tweak in the lab could make it work even better for more patients. The key is a natural immune protein called CD40L.

We discovered that by adding CD40L to the immune cells in the lab, we could dramatically improve the number and quality of cancer-fighting T cells we're able to grow. It's like flipping a switch that helps these cells become stronger and healthier."

Daniel Abate-Daga, Ph.D., scientific director of the Cell Therapies Core at Moffitt and lead author of the study

Results of the study showed that in more challenging specimens, TIL cultures grew successfully in 67% of samples when CD40L was used, compared to 33% without it. The approach also shaved up to one week off the manufacturing time, potentially getting the cellular immunotherapy to patients sooner. Finally, the enhanced cells were more "stem-like," a trait linked to longer-lasting cancer fighting capabilities.

"TIL therapy is one of the most promising treatments we have for solid tumors," said Abate-Daga. "This discovery could help more patients benefit and do so more quickly."

Moffitt is currently leading a clinical trial to test this approach in patients with non-small cell lung cancer. Researchers hope CD40L-enhanced TILs will become a next-generation standard in TIL therapy.

This study was funded by the National Cancer Institution (P30CA076292), the SuzyQ Melanoma Fund, Moffitt Cancer Center's Lung Cancer Center of Excellence and Donald A. Adam Skin Cancer and Melanoma Center of Excellence, the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation and the Mark Foundation ASPIRE program.