Notable Quotes:

“Currently, the REP phase is the step most amenable to closure by replacing the tissue culture flasks and bags with G-Rex 100MCS and GatheRex Cell Harvest Pump.”

“transition to G-Rex 100MCS flasks has resulted in fewer total vessels, less media, less incubator space and less labor than traditional culture methods using flasks and bags”

“Optimizing the TIL culture expansion allowed for consistent achievement of the optimal therapeutic dose of 60 x 10e9 cells for all patients compared with achievement of optimal dose in only 40% of patients using traditional culture methods”

Notable Quotes:

“High spare respiratory capacity is believed to be a feature of memory T cells that imparts them with better in vivo persistence, as opposed to effector T cells. We are thus postulating that the high spare respiratory capacity and the high OCR that we observed in TIL grown in high oxygen environment, more specifically the CD8+ BTLA+ cells, could therefore result in enhanced survival and persistence after transfer, which could confer better tumor control.”

“The G-Rex could favor expansion of less-differentiated cell subsets likely due to the availability of oxygen. High spare respiratory capacity is believed to be a feature of memory T-Cells"

“We also observed and reported that the use of the new flask impacted the phenotype of post expansion CD8C T cells, which had a consistently higher expression of a molecule previously associated with clinical response in our clinical trial”

“All together, the metabolic phenotype of melanoma TIL propagated in G-Rex was consistently more oxidative”

Adoptive cell therapy with autologous tumor-infiltrating lymphocytes (TIL) is a therapy for metastatic melanoma with response rates of up to 50%. However, the generation of the TIL
transfer product is challenging, requiring pooled allogeneic normal donor peripheral blood mononuclear cells (PBMC) used in vitro as “feeders” to support a rapid-expansion protocol. Here, we optimized a platform to propagate TIL to a clinical scale using K562 cells genetically modified to express costimulatory molecules such as CD86, CD137-ligand, and membrane-bound IL-15 to function as artificial antigen-presenting cells (aAPC) as an alternative to
using PBMC feeders.

Adoptive cell therapy of metastatic melanoma with autologous tumor infiltrating lymphocytes (TIL) is clinically effective, but TIL production can be challenging. Here we describe a simplified method for initial TIL culture and rapid expansion in gas-permeable flasks.