Cytotoxic T Lymphocytes Simultaneously Targeting Multiple Tumor-associated Antigens to Treat EBV Negative Lymphoma

被引：76

作者：

Gerdemann, Ulrike ^{[1
]}

Katari, Usha ^{[1
]}

Christin, Anne S. ^{[1
]}

Cruz, Conrad R. ^{[1
]}

Tripic, Tamara ^{[1
]}

Rousseau, Alexandra ^{[1
]}

Gottschalk, Stephen M. ^{[1
]}

Savoldo, Barbara ^{[1
]}

Vera, Juan F. ^{[1
]}

Heslop, Helen E. ^{[1
]}

Brenner, Malcolm K. ^{[1
]}

Bollard, Catherine M. ^{[1
]}

Rooney, Cliona M. ^{[1
]}

Leen, Ann M. ^{[1
]}

机构：

[1] Texas Childrens Hosp, Baylor Coll Med, Methodist Hosp, Ctr Cell & Gene Therapy, Houston, TX 77030 USA

来源：

MOLECULAR THERAPY | 2011年 / 19卷 / 12期

关键词：

CANCER TESTIS ANTIGEN; CELL RESPONSES; LYMPHOPROLIFERATIVE DISEASE; ADOPTIVE IMMUNOTHERAPY; PANCREATIC-CANCER; PRESENTING CELLS; IDENTIFICATION; EXPRESSION; THERAPY; EPITOPE;

D O I：

10.1038/mt.2011.167

中图分类号：

Q81 [生物工程学（生物技术）]; Q93 [微生物学];

学科分类号：

071005 ; 0836 ; 090102 ; 100705 ;

摘要：

Although immunotherapy with Epstein- Barr virus (EBV)specific cytotoxic T lymphocytes (CTLs) can treat EBV-associated Hodgkin and non-Hodgkin lymphoma (HL/NHL), more than 50% of such tumors are EBV negative. We now describe an approach that allows us to consistently generate, in a single line, CTLs that recognize a wide spectrum of nonviral tumor-associated antigens (TAAs) expressed by human HL/NHL, including Survivin, MAGE-A4, Synovial sarcoma X (SSX2), preferentially expressed antigen in melanoma (PRAME) and NY-ESO-1. We could generate these CTLs from nine of nine healthy donors and five of eight lymphoma patients, irrespective of human leukocyte antigen (HLA) type. We reactivated TAA-directed T cells ex vivo, by stimulation with dendritic cells (DCs) pulsed with overlapping peptide libraries spanning the chosen antigens in the presence of an optimized Th1-polarizing, prosurvival/proliferative and Treg inhibitory cytokine combination. The resultant lines of CD4(+) and CD8(+), polycytokine-producing T cells are directed against a multiplicity of epitopes expressed on the selected TAAs, with cytolytic activity against autologous tumor cells. Infusion of such multispecific monocultures may extend the benefits of CTL therapy to treatment even of EBV negative HL and NHL. Received 20 April 2011; accepted 18 July 2011; published online 13 September 2011. doi:10.1038/mt.2011.167

引用

页码：2258 / 2268

页数：11

共 49 条

[1]

Adida C, 2000, BLOOD, V96, P1921

[2] The universal character of the tumour-associated antigen survivin [J].