Specific Lymphocyte Subsets Predict Response to Adoptive Cell Therapy Using Expanded Autologous Tumor-Infiltrating Lymphocytes in Metastatic Melanoma Patients

被引：323

作者：

Radvanyi, Laszlo G. ^{[1
]}

Bernatchez, Chantale ^{[1
]}

Zhang, Minying ^{[1
]}

Fox, Patricia S. ^{[2
]}

Miller, Priscilla ^{[1
]}

Chacon, Jessica ^{[1
]}

Wu, Richard ^{[1
]}

Lizee, Gregory ^{[1
]}

Mahoney, Sandy ^{[1
]}

Alvarado, Gladys ^{[1
]}

Glass, Michelle ^{[1
]}

Johnson, Valen E. ^{[2
]}

McMannis, John D. ^{[3
]}

Shpall, Elizabeth ^{[3
]}

Prieto, Victor ^{[4
]}

Papadopoulos, Nicholas ^{[1
]}

Kim, Kevin ^{[1
]}

Homsi, Jade ^{[1
]}

Bedikian, Agop ^{[1
]}

Hwu, Wen-Jen ^{[1
]}

Patel, Sapna ^{[1
]}

Ross, Merrick I. ^{[5
]}

Lee, Jeffrey E. ^{[5
]}

Gershenwald, Jeffrey E. ^{[5
]}

Lucci, Anthony ^{[5
]}

Royal, Richard ^{[5
]}

Cormier, Janice N. ^{[5
]}

Davies, Michael A. ^{[1
]}

Mansaray, Rahmatu ^{[1
,3
]}

Fulbright, Orenthial J. ^{[1
,3
]}

Toth, Christopher ^{[1
,3
]}

Ramachandran, Renjith ^{[1
,3
]}

Wardell, Seth ^{[1
,3
]}

Gonzalez, Audrey ^{[1
,3
]}

Hwu, Patrick ^{[1
]}

机构：

[1] Univ Texas MD Anderson Canc Ctr, Dept Melanoma Med Oncol, Houston, TX 77030 USA

[2] Univ Texas MD Anderson Canc Ctr, Dept Biostat, Houston, TX 77030 USA

[3] Univ Texas MD Anderson Canc Ctr, Dept Stem Cell Transplant & Cellular Therapy, Houston, TX 77030 USA

[4] Univ Texas MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA

[5] Univ Texas MD Anderson Canc Ctr, Dept Surg Oncol, Houston, TX 77030 USA

来源：

CLINICAL CANCER RESEARCH | 2012年 / 18卷 / 24期

关键词：

CD8(+) T-CELLS; TELOMERE LENGTH; MEMORY; EFFECTOR; DIFFERENTIATION; COSTIMULATION; PERSISTENCE; INHIBITION; ACTIVATION; EXPRESSION;

D O I：

10.1158/1078-0432.CCR-12-1177

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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. Clin Cancer Res; 18(24); 6758-70. (C) 2012 AACR.

引用

页码：6758 / 6770

页数：13

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