Can Hybrid Immunotherapy Improve Solid Tumor Treatment?

Imagine if doctors could equip immune cells with a built-in GPS to locate hidden tumors and provide them with extra firepower to destroy them once they arrive. That’s the idea behind a new hybrid immunotherapy being developed at Moffitt Cancer Center. Researchers there have combined two powerful cancer-fighting strategies into one, and early results show promise in reaching solid tumors that have long resisted treatment. 

Two Immune Strategies in One

Chimeric antigen receptor T-cell therapy, also known as CAR T, has helped patients with certain blood cancers by reprogramming their immune cells to target specific cancer markers. But these cells often struggle to penetrate solid tumors, such as those found in lung, skin or pancreatic cancers. 

Daniel Abate-Daga, PhD

Tumor-infiltrating lymphocytes, or TILs, are another immune-based approach. TILs naturally travel into solid tumors, giving them an edge in treating cancers such as advanced melanoma. 

“CAR T cells are good at recognizing and attacking cancer but face barriers in getting inside solid tumors,” said Daniel Abate-Daga, PhD, an immunologist at Moffitt and the study’s lead author. “TILs have already shown benefit in several solid tumors, but they can lack the precision and power of CAR T cells. Our goal was to combine their strengths.” 

Early Results Show Promise

In the study, Moffitt scientists engineered TILs to express chimeric antigen receptors, turning them into CAR-TILs. This gave the cells both the navigation ability of TILs and the targeting accuracy of CAR T cells. 

When tested in laboratory models, CAR-TIL cells showed twice the tumor infiltration of standard CAR T cells and released higher levels of cancer fighting molecules. 

“These new CAR-TIL cells reached the tumor in higher numbers and showed more potent activity,” Abate-Daga said. “That’s exactly what is needed for these tough-to-treat cancers.” 

Why It Matters

Most U.S. Food and Drug Administration-approved CAR T-cell therapies are used for blood cancers, while TIL therapies are licensed for solid tumors such as melanoma. By merging the best features of both, Moffitt researchers hope CAR-TIL could expand the reach of cell therapy to more types of solid tumors. 

Additional studies are underway to test how well CAR-TIL cells can shrink tumors, moving the approach closer to future clinical trials. 

“This is just the beginning,” Abate-Daga said. “We’ve shown the concept works from a biological standpoint. The next step is to define its therapeutic impact and see how it performs in treating real patient tumors.”