Ex vivo enrichment of circulating anti-tumor T cells from both cutaneous and ocular melanoma patients: clinical implications for adoptive cell transfer therapy.

作者: Tonia Mazzarella , Valeria Cambiaghi , Nathalie Rizzo , Lorenzo Pilla , Danilo Parolini

DOI: 10.1007/S00262-011-1179-Z

关键词: ImmunotherapyEx vivoAdoptive cell transferMelanomaNKG2DLymphocyteImmunologyCutaneous melanomaMedicineOcular Melanoma

摘要: Tumor-infiltrating lymphocytes (TILs) have been successfully used for adoptive cell transfer (ACT) immunotherapy; however, due to their scarce availability, this therapy is possible a limited fraction of cutaneous melanoma patients. We assessed whether an effective protocol ex vivo T-cell expansion from peripheral blood mononuclear cells (PBMCs), suitable ACT both and ocular patients, could be identified. PBMCs patients were stimulated in vitro with autologous, irradiated (mixed lymphocyte tumor culture; MLTCs) the presence IL-2 IL-15 followed by rapid (REP). The functional activity these T was characterized compared that TILs. In addition, immune infiltration lesions analyzed. An efficient MLTC reactive achieved all PBMC’s samples obtained 7 metastatic Large numbers melanoma-specific when REP applied MLTCs. Most MLTCs enriched non-terminally differentiated TEM homogeneously expressing co-stimulatory molecules (e.g., NKG2D, CD28, CD134, CD137). A similar pattern anti-tumor activity, association more variable expression molecules, detected on short-term cultured TILs isolated same we observed infiltrate suppressive characteristics low rate growing (28.5% our cases). Our overcomes limitation, allowing isolation effector functions even Thus, circulating PBMC-derived efficiently novel enrichment protocol. This appears studies

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