Rapid expansion of tumor-reactive cells from HLA-matched siblings for adoptive immunotherapy of melanoma

作者: D.J. Gottlieb , K. Micklethwaite , K.F. Bradstock , Y-Ch Li

DOI: 10.1080/14653240601145231

关键词:

摘要: Background Administration of expanded tumor-infiltrating lymphocytes in association with lymphodepleting chemotherapy is effective some patients advanced malignant melanoma. However, obtaining and subsequent expansion labor intensive, making it impractical for broad clinical application. Allogeneic transplantation may have anti-melanoma efficacy because a graft vs. tumor effect. The disappointing control observed post-transplant suggests that adoptive immunotherapy using melanoma-reactive cells will be essential sustained responses. Methods Melanoma cell lines were grown from two disease. High-level CD80 CD86 expression was obtained the retroviral vector gene transfer. Transduced melanoma controls cultured mononuclear HLA-identical sibling donors. Results Expression CD86, particularly former, promoted marked HLA-matched Proliferation up to 300-fold after 4 weeks culture observed. Lymphocytes cultures stimulated demonstrated cytotoxicity against recipient-untransfected (45–75% specific lysis at an E:T ratio 50:1). Although predominantly CD4 + , greatest numerically smaller CD8 subpopulation. Both secreted IFN-γ (but not IL-4) on exposure untransduced stimulator cells. Discussion Our strategy generates large number siblings 4-week strategy. this way offer alternative allogeneic cellular stem young patients.

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