CD8+ Enriched "Young" Tumor Infiltrating Lymphocytes Can Mediate Regression of Metastatic Melanoma

被引：245

作者：

Dudley, Mark E. ^{[1
]}

Gross, Colin A. ^{[1
]}

Langhan, Michelle M. ^{[1
]}

Garcia, Marcos R. ^{[1
]}

Sherry, Richard M. ^{[1
]}

Yang, James C. ^{[1
]}

Phan, Giao Q. ^{[1
]}

Kammula, Udai S. ^{[1
]}

Hughes, Marybeth S. ^{[1
]}

Citrin, Deborah E. ^{[2
]}

Restifo, Nicholas P. ^{[1
]}

Wunderlich, John R. ^{[1
]}

Prieto, Peter A. ^{[1
]}

Hong, Jenny J. ^{[1
]}

Langan, Russell C. ^{[1
]}

Zlott, Daniel A. ^{[3
]}

Morton, Kathleen E. ^{[1
]}

White, Donald E. ^{[1
]}

Laurencot, Carolyn M. ^{[1
]}

Rosenberg, Steven A. ^{[1
]}

机构：

[1] NCI, Surg Branch, Bethesda, MD 20892 USA

[2] NCI, Radiat Oncol Branch, Bethesda, MD 20892 USA

[3] NIH, Dept Pharm, Clin Res Ctr, Bethesda, MD 20892 USA

来源：

CLINICAL CANCER RESEARCH | 2010年 / 16卷 / 24期

关键词：

CD8(+) T-CELLS; TRANSFER THERAPY; CD8-T-CELL MEMORY; ADOPTIVE TRANSFER; CD4-T-CELL HELP; CANCER; SURVIVAL; PERSISTENCE; IMMUNOTHERAPY; AUTOIMMUNITY;

D O I：

10.1158/1078-0432.CCR-10-1297

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Purpose: Tumor-infiltrating lymphocytes (TIL) and interleukin (IL)-2 administered following lymphodepletion can cause the durable complete regression of bulky metastatic melanoma in patients refractory to approved treatments. However, the generation of a unique tumor-reactive TIL culture for each patient may be prohibitively difficult. We therefore investigated the clinical and immunologic impact of unscreened, CD8+ enriched "young" TIL. Experimental Design: Methods were developed for generating TIL that minimized the time in culture and eliminated the individualized tumor-reactivity screening step. Thirty-three patients were treated with these CD8+ enriched young TIL and IL-2 following nonmyeloablative lymphodepletion (NMA). Twenty-three additional patients were treated with CD8+ enriched young TIL and IL-2 after lymphodepletion with NMA and 6 Gy of total body irradiation. Results: Young TIL cultures for therapy were successfully established from 83% of 122 consecutive melanoma patients. Nineteen of 33 patients (58%) treated with CD8+ enriched young TIL and NMA had an objective response (Response Evaluation Criteria in Solid Tumors) including 3 complete responders. Eleven of 23 patients (48%) treated with TIL and 6 Gy total body irradiation had an objective response including 2 complete responders. At 1 month after TIL infusion the absolute CD8+ cell numbers in the periphery were highly correlated with response. Conclusions: This study shows that a rapid and simplified method can be used to reliably generate CD8+ enriched young TIL for administration as an individualized therapy for advanced melanoma, and may allow this potentially effective treatment to be applied at other institutions and to reach additional patients. Clin Cancer Res; 16(24); 6122-31. (C) 2010 AACR.

引用

页码：6122 / 6131

页数：10

共 31 条

[1] CD8+T cell immunity against a tumor/self-antigen is augmented by CD4+ T helper cells and hindered by naturally occurring T regulatory cells [J].

Antony, PA ;

Piccirillo, CA ;

Akpinarli, A ;

Finkelstein, SE ;

Speiss, PJ ;

Surman, DR ;

Palmer, DC ;

Chan, CC ;

Klebanoff, CA ;

Overwijk, WW ;

Rosenberg, SA ;

Restifo, NP .

JOURNAL OF IMMUNOLOGY, 2005, 174 (05) :2591-2601

[2] Clinical Responses in a Phase II Study Using Adoptive Transfer of Short-term Cultured Tumor Infiltration Lymphocytes in Metastatic Melanoma Patients [J].

Besser, Michal J. ;

Shapira-Frommer, Ronnie ;

Treves, Avraham J. ;

Zippel, Dov ;

Itzhaki, Orit ;

Hershkovitz, Liat ;

Levy, Daphna ;

Kubi, Adva ;

Hovav, Einat ;

Chermoshniuk, Natalia ;

Shalmon, Bruria ;

Hardan, Izhar ;

Catane, Raphael ;

Markel, Gal ;

Apter, Sara ;

Ben-Nun, Alon ;

Kuchuk, Iryna ;

Shimoni, Avichai ;

Nagler, Arnon ;

Schachter, Jacob .

CLINICAL CANCER RESEARCH, 2010, 16 (09) :2646-2655

[3] Minimally Cultured or Selected Autologous Tumor-infiltrating Lymphocytes After a Lympho-depleting Chemotherapy Regimen in Metastatic Melanoma Patients [J].

Besser, Michal J. ;

Shapira-Frommer, Ronnie ;

Treves, Avraham J. ;

Zippel, Dov ;

Itzhaki, Orit ;

Schallmach, Ester ;

Kubi, Adva ;

Shalmon, Bruria ;

Hardan, Izhar ;

Catane, Raphael ;

Segal, Eran ;

Markel, Gal ;

Apter, Sara ;

Ben Nun, Alon ;

Kuchuk, Iryna ;

Shimoni, Avichai ;

Nagler, Arnon ;

Schachter, Jacob .

JOURNAL OF IMMUNOTHERAPY, 2009, 32 (04) :415-423

[4] Tumor-Associated Lymphocytes As an Independent Predictor of Response to Neoadjuvant Chemotherapy in Breast Cancer [J].

Denkert, Carsten ;

Loibl, Sibylle ;

Noske, Aurelia ;

Roller, Marc ;

Mueller, Berit Maria ;

Komor, Martina ;

Budczies, Jan ;

Darb-Esfahani, Silvia ;

Kronenwett, Ralf ;

Hanusch, Claus ;

von Toerne, Christian ;

Weichert, Wilko ;

Engels, Knut ;

Solbach, Christine ;

Schrader, Iris ;

Dietel, Manfred ;

von Minckwitz, Gunter .

JOURNAL OF CLINICAL ONCOLOGY, 2010, 28 (01) :105-113

[5] Adoptive Cell Therapy for Patients With Metastatic Melanoma: Evaluation of Intensive Myeloablative Chemoradiation Preparative Regimens [J].

Dudley, Mark E. ;

Yang, James C. ;

Sherry, Richard ;

Hughes, Marybeth S. ;

Royal, Richard ;

Kammula, Udai ;

Robbins, Paul F. ;

Huang, JianPing ;

Citrin, Deborah E. ;

Leitman, Susan F. ;

Wunderlich, John ;

Restifo, Nicholas P. ;

Thomasian, Armen ;

Downey, Stephanie G. ;

Smith, Franz O. ;

Klapper, Jacob ;

Morton, Kathleen ;

Laurencot, Carolyn ;

White, Donald E. ;

Rosenberg, Steven A. .

JOURNAL OF CLINICAL ONCOLOGY, 2008, 26 (32) :5233-5239

[6] Adoptive cell transfer therapy following non-myeloablative but lymphodepleting chemotherapy for the treatment of patients with refractory metastatic melanoma [J].

Dudley, ME ;

Wunderlich, JR ;

Yang, JC ;

Sherry, RM ;

Topalian, SL ;

Restifo, NP ;

Royal, RE ;

Kammula, U ;

White, DE ;

Mavroukakis, SA ;

Rogers, LJ ;

Gracia, GJ ;

Jones, SA ;

Mangiameli, DP ;

Pelletier, MM ;

Gea-Banacloche, J ;

Robinson, MR ;

Berman, DM ;

Filie, AC ;

Abati, A ;

Rosenberg, SA .

JOURNAL OF CLINICAL ONCOLOGY, 2005, 23 (10) :2346-2357

[7] Generation of tumor-infiltrating lymphocyte cultures for use in adoptive transfer therapy for melanoma patients [J].

Dudley, ME ;

Wunderlich, JR ;

Shelton, TE ;

Even, J ;

Rosenberg, SA .

JOURNAL OF IMMUNOTHERAPY, 2003, 26 (04) :332-342

[8] Removal of homeostatic cytokine sinks by lymphodepletion enhances the efficacy of adoptively transferred tumor-specific CD8+ T cells [J].

Gattinoni, L ;

Finkelstein, SE ;

Klebanoff, CA ;

Antony, PA ;

Palmer, DC ;

Spiess, PJ ;

Hwang, LN ;

Yu, ZY ;

Wrzesinski, C ;

Heimann, DM ;

Surh, CD ;

Rosenberg, SA ;

Restifo, NP .

JOURNAL OF EXPERIMENTAL MEDICINE, 2005, 202 (07) :907-912

[9] Tumor Infiltrating Lymphocyte Therapy for Metastatic Melanoma: Analysis of Tumors Resected for TIL [J].

Goff, Stephanie L. ;

Smith, Franz O. ;

Klapper, Jacob A. ;

Sherry, Richard ;

Wunderlich, John R. ;

Steinberg, Seth M. ;

White, Donald ;

Rosenberg, Steven A. ;

Dudley, Mark E. ;

Yang, James C. .

JOURNAL OF IMMUNOTHERAPY, 2010, 33 (08) :840-847

[10] Improved Survival with Ipilimumab in Patients with Metastatic Melanoma [J].

Hodi, F. Stephen ;

O'Day, Steven J. ;

McDermott, David F. ;

Weber, Robert W. ;

Sosman, Jeffrey A. ;

Haanen, John B. ;

Gonzalez, Rene ;

Robert, Caroline ;

Schadendorf, Dirk ;

Hassel, Jessica C. ;

Akerley, Wallace ;

van den Eertwegh, Alfons J. M. ;

Lutzky, Jose ;

Lorigan, Paul ;

Vaubel, Julia M. ;

Linette, Gerald P. ;

Hogg, David ;

Ottensmeier, Christian H. ;

Lebbe, Celeste ;

Peschel, Christian ;

Quirt, Ian ;

Clark, Joseph I. ;

Wolchok, Jedd D. ;

Weber, Jeffrey S. ;

Tian, Jason ;

Yellin, Michael J. ;

Nichol, Geoffrey M. ;

Hoos, Axel ;

Urba, Walter J. .

NEW ENGLAND JOURNAL OF MEDICINE, 2010, 363 (08) :711-723

← 1 2 3 4 →