Hello everyone,
I was wondering, since i read a lot of protocols about TIL expansion from solid tumors, what is the specific function of feeder cells for TIL expansion and why are they used in most of the protocols? Could i expand TILs without using feeder cells or they are a must. I will be very grateful if you share with me some articles on that matter.
Thank you for your time.
Hello Veselina D.Nikolova
TIL expansion mostly uses rapid-expansion protocol (REP) using CD3 cross-linking and IL-2 after an initial expansion of TIL from small pieces of tumor (tumor fragments) with IL-2 alone. A key component in the REP besides anti-CD3 and IL-2 is the presence of an excess of irradiated allogeneic peripheral blood mononuclear cells (PBMC) from healthy donors added as “feeder cells”. These feeders are needed to support TIL activation and propagation early during the REP.
Basically, the feeder cells (PBMCs) help in activation of TILs with shorter time in culture. In TIL therapy, TILs are collected from the tumor during a biopsy, or a surgical resection, and grown to very large numbers in a laboratory with interleukin-2 (IL-2), a protein that promotes rapid TIL growth. This process typically takes several weeks but can be shortened if feeder cells are used. Once successfully grown to billions in number, the TILs are infused back into the patient, where they actively attack cancer cells while leaving healthy cells alone.
However, the procurement of large numbers of feeder cells (PBMCs) is difficult and expensive. The practicality of using these feeders is further compounded by the requirement to pool PBMCs from multiple donors to ensure optimal activity, which in turn introduces lot-to-lot heterogeneity and variability in activation of TIL.
To overcome this problem, artificial antigen presenting cells (aAPCs) expressing ligands for the T cell receptor and costimulatory molecules can activate and expand T cells for transfer, while improving their potency and function.
You may refer to the research article attached where the investigators make use of engineered K562 cell-based aAPCs as an "off-the-shelf" platform for ex vivo TIL expansion. K562 aAPCs that express CD137L offer the potential to expand antigen-experienced TILs and represent a potential new cell-based platform for the standardization of ex vivo TIL expansion.
Article Engineered artificial antigen presenting cells facilitate di...
Best.
Dear Malcolm Nobre,
I sincerely appreciate your comprehensive response. It was very helpful.
Have a wonderful day!
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