Establishment and large-scale expansion of minimally cultured "young" XXXX infiltrating lymphocytes for adoptive transfer therapy.

@entity1 @entity5 @entity405 @entity320
Treatment of @entity320 @entity1 with adoptively transferred @entity5 infiltrating lymphocytes (TIL) has developed into an effective therapy. Various studies reported objective responses of 50% and more. The use of unselected, minimally cultured, bulk TIL (Young-TIL) has simplified the TIL production process and may therefore, allow the accessibility of this approach to @entity5 centers worldwide. This article describes the precise process leading to the large-scale production of Young-TIL for therapy. We have enrolled 55 @entity320 @entity1 and optimized their Young-TIL generation process. Young-TIL cultures were successfully established for 51 of 55 (93%) @entity1 in 16.7    5.5 days. In a large-scale expansion procedure Young-TIL of 32 @entity1 were further expanded to treatment levels, resulting in a final number of 4.5 x 10         2.0 x 10      TIL. Fifteen of 31 (48%) @entity1 , who were evaluated, achieved a clinical response, including 4 complete and 11 partial responses. We confirmed the significant correlation between short culture duration, high number of infused cells, and @entity5 regression. A high percentage of @entity405 T cells in the infusion product was beneficial to achieve an objective response. All responding @entity1 were treated with Young-TIL cultures established in < 20 days. In summary, we describe here an efficient and reliable method to generate Young-TIL for adoptive transfer therapy, which may easily be adopted by other @entity5 centers and can lead to objective responses in 50% of refractory @entity320 @entity1 . In the future this approach may be used also in other types of @entity5 .
