TY - JOUR
T1 - Specific lymphocyte subsets predict response to adoptive cell therapy using expanded autologous tumor-infiltrating lymphocytes in metastatic melanoma patients
AU - Radvanyi, Laszlo G.
AU - Bernatchez, Chantale
AU - Zhang, Minying
AU - Fox, Patricia S.
AU - Miller, Priscilla
AU - Chacon, Jessica
AU - Wu, Richard
AU - Lizee, Gregory
AU - Mahoney, Sandy
AU - Alvarado, Gladys
AU - Glass, Michelle
AU - Johnson, Valen E.
AU - McMannis, John D.
AU - Shpall, Elizabeth
AU - Prieto, Victor
AU - Papadopoulos, Nicholas
AU - Kim, Kevin
AU - Homsi, Jade
AU - Bedikian, Agop
AU - Hwu, Wen Jen
AU - Patel, Sapna
AU - Ross, Merrick I.
AU - Lee, Jeffrey E.
AU - Gershenwald, Jeffrey E.
AU - Lucci, Anthony
AU - Royal, Richard
AU - Cormier, Janice N.
AU - Davies, Michael A.
AU - Mansaray, Rahmatu
AU - Fulbright, Orenthial J.
AU - Toth, Christopher
AU - Ramachandran, Renjith
AU - Wardell, Seth
AU - Gonzalez, Audrey
AU - Hwu, Patrick
PY - 2012/12/15
Y1 - 2012/12/15
N2 - Purpose: Adoptive cell therapy (ACT) using autologous tumor-infiltrating lymphocytes (TIL) is a promising treatment for metastatic melanoma unresponsive to conventional therapies. We report here on the results of an ongoing phase II clinical trial testing the efficacy of ACT using TIL in patients with metastatic melanoma and the association of specific patient clinical characteristics and the phenotypic attributes of the infused TIL with clinical response. Experimental Design: Altogether, 31 transiently lymphodepleted patients were treated with their expanded TIL, followed by two cycles of high-dose interleukin (IL)-2 therapy. The effects of patient clinical features and the phenotypes of the T cells infused on the clinical response were determined. Results: Overall, 15 of 31 (48.4%) patients had an objective clinical response using immune-related response criteria (irRC) with 2 patients (6.5%) having a complete response. Progression-free survival of more than 12 months was observed for 9 of 15 (60%) of the responding patients. Factors significantly associated with the objective tumor regression included a higher number of TIL infused, a higher proportion of CD8+ T cells in the infusion product, a more differentiated effector phenotype of the CD8+ population, and a higher frequency of CD8+ T cells coexpressing the negative costimulation molecule "B- and T-lymphocyte attenuator" (BTLA). No significant difference in the telomere lengths of TIL between responders and nonresponders was identified. Conclusion: These results indicate that the immunotherapy with expanded autologous TIL is capable of achieving durable clinical responses in patients with metastatic melanoma and that CD8+ T cells in the infused TIL, particularly differentiated effectors cells and cells expressing BTLA, are associated with tumor regression.
AB - Purpose: Adoptive cell therapy (ACT) using autologous tumor-infiltrating lymphocytes (TIL) is a promising treatment for metastatic melanoma unresponsive to conventional therapies. We report here on the results of an ongoing phase II clinical trial testing the efficacy of ACT using TIL in patients with metastatic melanoma and the association of specific patient clinical characteristics and the phenotypic attributes of the infused TIL with clinical response. Experimental Design: Altogether, 31 transiently lymphodepleted patients were treated with their expanded TIL, followed by two cycles of high-dose interleukin (IL)-2 therapy. The effects of patient clinical features and the phenotypes of the T cells infused on the clinical response were determined. Results: Overall, 15 of 31 (48.4%) patients had an objective clinical response using immune-related response criteria (irRC) with 2 patients (6.5%) having a complete response. Progression-free survival of more than 12 months was observed for 9 of 15 (60%) of the responding patients. Factors significantly associated with the objective tumor regression included a higher number of TIL infused, a higher proportion of CD8+ T cells in the infusion product, a more differentiated effector phenotype of the CD8+ population, and a higher frequency of CD8+ T cells coexpressing the negative costimulation molecule "B- and T-lymphocyte attenuator" (BTLA). No significant difference in the telomere lengths of TIL between responders and nonresponders was identified. Conclusion: These results indicate that the immunotherapy with expanded autologous TIL is capable of achieving durable clinical responses in patients with metastatic melanoma and that CD8+ T cells in the infused TIL, particularly differentiated effectors cells and cells expressing BTLA, are associated with tumor regression.
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U2 - 10.1158/1078-0432.CCR-12-1177
DO - 10.1158/1078-0432.CCR-12-1177
M3 - Article
C2 - 23032743
AN - SCOPUS:84871207055
SN - 1078-0432
VL - 18
SP - 6758
EP - 6770
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 24
ER -