T cells activated in vitro as immunotherapy for renal, cell carcinoma: Characterization of 2 effector T-cell populations

被引:3
作者
Garlie, NK [1 ]
Siebenlist, RE [1 ]
Lefever, AV [1 ]
机构
[1] St Lukes Med Ctr, Immunotherapy Program, Milwaukee, WI 53201 USA
关键词
carcinoma; renal cell; T-lymphocytes; immunotherapy; adoptive;
D O I
10.1016/S0022-5347(05)66149-6
中图分类号
R5 [内科学]; R69 [泌尿科学(泌尿生殖系疾病)];
学科分类号
1002 ; 100201 ;
摘要
Purpose: Effector T cell populations generated using 2 methods of in vitro activation are currently being tested in separate clinical trials as immunotherapy for patients with advanced cancer, including renal cell carcinoma. To determine the most appropriate method of activation for cancer immunotherapy in vitro antitumor activity of the 2 effector T-cell populations were compared. Materials and Methods: The effector T-cell populations were generated concurrently by activation of peripheral blood mononuclear cells from patients with advanced renal cell carcinoma or other cancer using soluble anti-CDS monoclonal antibody (3T cells) or anti-CD3 and anti-CD28 monoclonal antibodies immobilized on beads (3/28T cells). After 14-day culture the phenotype and functional activity of the cells were tested. Results: Fold expansion of CD4(+) cells for 3T cultures was lower than for 3/28T cultures but expansion of CD8(+) cells was similar for both cultures. Expression of CD69 was higher on 3T cells. 3T and 3/28T cells exhibited similar ability to kill various human tumor cell lines. Although both effector T-cell populations produced Th1-type cytokines upon re-stimulation, 3T cells secreted a higher level of interferon-gamma and tumor necrosis factor-a compared with 3/28T cells. Intracellular cytokine analysis demonstrated that the percent of cells producing interferon-gamma was higher in CD4(+), CD8(+), CD25(+), CD69(+) and CD45RO(+) 3T cells compared with 3/28T cells. Conclusions: These data suggest that 3T cells may have increased efficacy as immunotherapy for patients with cancer due to higher levels of tumoricidal cytokine production than 3/28T cells.
引用
收藏
页码:299 / 303
页数:5
相关论文
共 24 条
[1]   Tumor-specific granulocyte macrophage colony-stimulating factor and interferon gamma secretion is associated with in vivo therapeutic efficacy of activated tumor-draining lymph node cells [J].
Aruga, A ;
Shu, SY ;
Chang, AE .
CANCER IMMUNOLOGY IMMUNOTHERAPY, 1995, 41 (05) :317-324
[2]   T-LYMPHOCYTE-DIRECTED GENE-THERAPY FOR ADA(-) SCID - INITIAL TRIAL RESULTS AFTER 4 YEARS [J].
BLAESE, RM ;
CULVER, KW ;
MILLER, AD ;
CARTER, CS ;
FLEISHER, T ;
CLERICI, M ;
SHEARER, G ;
CHANG, L ;
CHIANG, YW ;
TOLSTOSHEV, P ;
GREENBLATT, JJ ;
ROSENBERG, SA ;
KLEIN, H ;
BERGER, M ;
MULLEN, CA ;
RAMSEY, WJ ;
MUUL, L ;
MORGAN, RA ;
ANDERSON, WF .
SCIENCE, 1995, 270 (5235) :475-480
[3]   CD28 COSTIMULATION CAN PROMOTE T-CELL SURVIVAL BY ENHANCING THE EXPRESSION OF BCL-X(L) [J].
BOISE, LH ;
MINN, AJ ;
NOEL, PJ ;
JUNE, CH ;
ACCAVITTI, MA ;
LINDSTEN, T ;
THOMPSON, CB .
IMMUNITY, 1995, 3 (01) :87-98
[4]   THE CD2 AND CD28 ADHESION MOLECULES INDUCE LONG-TERM AUTOCRINE PROLIFERATION OF CD4+ T-CELLS [J].
COSTELLO, R ;
CERDAN, C ;
PAVON, C ;
BRAILLY, H ;
HURPIN, C ;
MAWAS, C ;
OLIVE, D .
EUROPEAN JOURNAL OF IMMUNOLOGY, 1993, 23 (03) :608-613
[5]   Influence of interleukin-2 regimens on circulating populations of lymphocytes after adoptive transfer of anti-CD3-stimulated T cells: Results from a phase I trial in cancer patients [J].
Curti, BD ;
Ochoa, AC ;
Urba, WJ ;
Alvord, WG ;
Kopp, WC ;
Powers, G ;
Hawk, C ;
Creekmore, SP ;
Gause, BL ;
Janik, JE ;
Holmlund, JT ;
Kremers, P ;
Fenton, RG ;
Miller, L ;
Sznol, S ;
Smith, JW ;
Sharfman, WH ;
Longo, DL .
JOURNAL OF IMMUNOTHERAPY, 1996, 19 (04) :296-308
[6]   Phase I trial of anti-CD3-stimulated CD4+ T cells infusional interleukin-2, and cyclophosphamide in patients with advanced cancer [J].
Curti, BD ;
Ochoa, AC ;
Powers, GC ;
Kopp, WC ;
Alvord, WG ;
Janik, JE ;
Gause, BL ;
Dunn, B ;
Kopreski, MS ;
Fenton, R ;
Zea, A ;
Dansky-Ullmann, C ;
Strobl, S ;
Harvey, L ;
Nelson, E ;
Sznol, M ;
Longo, DL .
JOURNAL OF CLINICAL ONCOLOGY, 1998, 16 (08) :2752-2760
[7]  
DELIA D, 1988, IMMUNOLOGY, V64, P593
[8]   T cells coactivated with immobilized anti-CD3 and anti-CD28 as potential immunotherapy for cancer [J].
Garlie, NK ;
LeFever, AV ;
Siebenlist, RE ;
Levine, BL ;
June, CH ;
Lum, LG .
JOURNAL OF IMMUNOTHERAPY, 1999, 22 (04) :336-345
[9]   REACTIVATION OF MURINE TUMOR-INFILTRATING LYMPHOCYTES WITH SOLID-PHASE ANTI-CD3 ANTIBODY - IN-VITRO CYTOKINE PRODUCTION IS ASSOCIATED WITH IN-VIVO EFFICACY [J].
GOEDEGEBUURE, PS ;
ZUBER, M ;
LEONARDVIDAL, DL ;
BURGER, UL ;
CUSACK, JC ;
CHANG, MP ;
DOUVILLE, LM ;
EBERLEIN, TJ .
SURGICAL ONCOLOGY-OXFORD, 1994, 3 (02) :79-89
[10]  
Hoffman DMJ, 2000, SEMIN ONCOL, V27, P221