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,” said Daniel Abate-Daga, Ph.D., scientific director of the Cell Therapies Core at Moffitt and lead author of the study. “It’s like flipping a switch that helps these cells become stronger and healthier.”

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.

Immune cell composition of melanoma tumors and response to CD40L

Melanoma digests were cultured in standard TIL expansion media (control) or supplemented with an agonist of CD40 (CD40L) for 48 hours (n=14 samples, 7 patients) and analyzed by single-cell RNA sequencing. (A) UMAP projection of different cell populations identified in the tumor digests. (B) UMAP projection of the tumor digests based on culture conditions (CD40L vs control). (C) UMAP projection of B-cells, showing expression of IgA, IgD, IgE, IgG1, IgG2, IgG3, IgG4 and IgM antibody/BCR isotypes. (D) UMAP projection of B-cells showing subclusters identified by the Seurat algorithm. Clusters corresponding to CD40L-treated samples are indicated with the red square. (E) Cross-referencing of B-cell clusters with previously described gene sets corresponding to naive, memory, germinal center (GC) and plasma cells. TIL, tumor-infiltrating lymphocyte.

“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.

Source – Moffitt Cancer Center