A research team from the Senior Department of Oncology of Chinese PLA General Hospital and Shanghai Juncell Therapeutics announced on July 3 the development of a feeder-free tumor-infiltrating lymphocyte (TIL) expansion system designed to make advanced cancer immunotherapy safer and more accessible. The new approach, published in Cancer Biology & Medicine, aims to address challenges associated with conventional TIL therapy, which often requires high-dose interleukin-2 (IL-2) and feeder cells that can complicate manufacturing and increase toxicity risks.
The researchers developed a two-phase protocol that eliminates the need for feeder cells by using low concentrations of IL-2 along with other cytokines such as IL-7 and IL-15 during initial cell culture. In the rapid expansion phase, an even lower concentration of IL-2 is used together with CD3/CD28 co-stimulation. This method reportedly achieved at least a 90% success rate in expanding functional TILs across several solid tumor types including melanoma, pancreatic, gastric, cervical, and colorectal cancers. Melanoma-derived TILs expanded approximately 2,500-fold using this technique.
According to the study authors, "Our goal was to eliminate TIL therapy's dependency on high-dose IL-2, which has been a major barrier to broader clinical use. By creating a feeder-free system with carefully calibrated cytokine support, we've shown that we can generate functional, less exhausted TILs from multiple tumor types. The addition of low-dose PD-1 blockade not only boosted anti-tumor efficacy but also improved treatment tolerability, as mice in the combination group maintained better health and avoided the ulceration observed with TILs alone. While HCQ showed intriguing immunomodulatory effects, its in vivo benefit was limited in this small study. We believe this feeder-free, IL-2-sparing strategy has real potential to make TIL therapy safer and more widely available for patients with solid tumors."
The expanded TIL products demonstrated high purity—over 93% CD45+CD3+ cells—and strong cytotoxic activity marked by interferon-gamma secretion and effective tumor cell killing dependent on effector-to-target ratios. Notably, these cells showed minimal exhaustion markers such as PD-1 expression below 0.5%, suggesting improved function compared to standard protocols.
The study also investigated combining low-dose PD-1 blockade or hydroxychloroquine (HCQ) as complementary strategies. In a colorectal cancer patient-derived xenograft model in mice, adding low-dose PD-1 inhibitor significantly reduced tumor volume compared to controls while preventing ulceration seen in other groups; HCQ increased MHC-I expression on tumor cells without affecting programmed death-ligand 1 levels or impairing T-cell proliferation.
Researchers said these findings could simplify manufacturing processes for cellular therapies by eliminating feeder cells and reducing reliance on high-dose cytokines—potentially lowering costs and increasing availability beyond specialized centers. Future studies are planned to further validate these results across larger models and diverse cancers.
