RE:RE:RE:CD8+ TiLs and T-cell exhaustionApril 21, 2024 - "It took more than 35 years for tumor-infiltrating lymphocytes, which Steven A. Rosenberg, MD, PhD, and colleagues first reported on in 1988 for the treatment of advanced melanoma, to progress enough to gain FDA approval."
As physicians, researchers and patients celebrated the FDA approval for lifileucel (Amtagvi, Iovance Biotherapeutics) in February, Rosenberg had long started work on the future of tumor-infiltrating lymphocytes (TILs)..
Another strategy under investigation involves inducing TILs in tumors that do not produce them. “[Researchers] are looking at oncolytic viruses, which they say turn a cold tumor into a hot tumor, to determine whether that maneuver will generate TILs that you can then [harvest] from the tumor, expand and give back to patients,” James J. Mul, IPhD, immunologist and associate center director of translational science at Moffitt Cancer Center, said.
George Ansstas, MD, associate professor at Washington University in St. Louis and leader of the solid tumor TIL program at Siteman Cancer Center. discussed research into moving TILs up in the treatment regimen with checkpoint inhibitors, or the best combination with TILs in the latter stages of treatment to improve response.
“One of the thoughts is, for example, adding PD-L1 and LAG3 — other immune checkpoint inhibitors that could really activate these TILs,” Ansstas said. “We need to investigate what is suppressing these T cells, and see what immune checkpoint inhibitors are being expressed, and try to target [them].”
https://www.healio.com/news/hematology-oncology/20240418/lifileucel-approval-the-start-of-a-glorious-future-for-cell-therapy-in-solid-tumors
Iovance Biotherapeutics' PDUFA date was February 24, 2024 demonstrating that the approval of its tumor infiltrating lymphocyte (TIL) therapy serves to confirm ONCY's pelareorep critical effect on the increase of CD8+ TiLs cells as significant mediators of cytotoxic effector function in the treatment of cancer,
As posted earlier, high levels of PD-1 expression contribute to the characteristic dysfunction seen in exhausted CD8+ TiL cells. Correspondingly, in human tumors, a higher proportion of progenitor exhausted cells was associated with a greater likelihood of response to checkpoint blockade. While PD-1 blockade therapies have been successful in multiple tumor types, their effectiveness has been limited to between 10-20% of the patients treated.
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