BACKGROUND: Adoptive immunotherapy for patients with metastatic melanoma has yielded encouraging results. However, methods of expanding melanoma-specific T cells from stage III are limited. The objective of this study was to determine whether melanoma-specific T cells could be generated from the melanoma-draining lymph nodes (MDLNs) of patients in stage III. METHODS: Patients in stage III who were undergoing completion lymphadenectomy were enrolled into a protocol approved by the institutional review board. MDLN cells were tested for ability to undergo cryopreservation, expand ex vivo in IL-2 or IL-2 and IL-7, and mediate melanoma-specific antitumor responses in vitro. RESULTS: Cryopreservation produced no significant differences from fresh cultures in terms of cell growth and cellular phenotype. IL-2 and IL-2/IL-7 cultures resulted in similar growth rates, and functional studies revealed the presence of T cells that secreted interferon gamma in response to melanoma antigen peptides. Both IL-2- and IL-2/IL-7-cultured MDLN cells mediated significant apoptosis of human melanoma cell lines as compared to breast and brain tumor lines in vitro. Overall, there did not seem to be a benefit of adding IL-7. Both CD4+ and CD8+ T cells appear to mediate tumor cell apoptosis. CONCLUSION: This study demonstrates that melanoma antigen-specific T cells can be generated from regional melanoma-draining lymph nodes and expanded ex vivo from patients with stage III disease.
BACKGROUND: Adoptive immunotherapy for patients with metastatic melanoma has yielded encouraging results. However, methods of expanding melanoma-specific T cells from stage III are limited. The objective of this study was to determine whether melanoma-specific T cells could be generated from the melanoma-draining lymph nodes (MDLNs) of patients in stage III. METHODS:Patients in stage III who were undergoing completion lymphadenectomy were enrolled into a protocol approved by the institutional review board. MDLN cells were tested for ability to undergo cryopreservation, expand ex vivo in IL-2 or IL-2 and IL-7, and mediate melanoma-specific antitumor responses in vitro. RESULTS: Cryopreservation produced no significant differences from fresh cultures in terms of cell growth and cellular phenotype. IL-2 and IL-2/IL-7 cultures resulted in similar growth rates, and functional studies revealed the presence of T cells that secreted interferon gamma in response to melanoma antigen peptides. Both IL-2- and IL-2/IL-7-cultured MDLN cells mediated significant apoptosis of humanmelanoma cell lines as compared to breast and brain tumor lines in vitro. Overall, there did not seem to be a benefit of adding IL-7. Both CD4+ and CD8+ T cells appear to mediate tumor cell apoptosis. CONCLUSION: This study demonstrates that melanoma antigen-specific T cells can be generated from regional melanoma-draining lymph nodes and expanded ex vivo from patients with stage III disease.
Authors: Naomi N Hunder; Herschel Wallen; Jianhong Cao; Deborah W Hendricks; John Z Reilly; Rebecca Rodmyre; Achim Jungbluth; Sacha Gnjatic; John A Thompson; Cassian Yee Journal: N Engl J Med Date: 2008-06-19 Impact factor: 91.245
Authors: W C To; B G Wood; J C Krauss; M Strome; R M Esclamado; P Lavertu; D Dasko; J A Kim; G E Plautz; B E Leff; V Smith; K Sandstrom-Wakeling; S Shu Journal: Arch Otolaryngol Head Neck Surg Date: 2000-10
Authors: L Tramsen; U Koehl; T Tonn; J-P Latgé; F R Schuster; A Borkhardt; L Uharek; R Quaritsch; O Beck; E Seifried; T Klingebiel; T Lehrnbecher Journal: Bone Marrow Transplant Date: 2008-09-01 Impact factor: 5.483
Authors: Li-Xin Wang; Wen-Xin Huang; Hallie Graor; Peter A Cohen; Julian A Kim; Suyu Shu; Gregory E Plautz Journal: J Transl Med Date: 2004-11-26 Impact factor: 5.531