Expansion of cytotoxic CD3+CD56+ cells from peripheral blood progenitor cells of patients undergoing autologous hematopoietic cell transplantation

被引:112
作者
Alvarnas, JC [1 ]
Linn, YC [1 ]
Hope, EG [1 ]
Negrin, RS [1 ]
机构
[1] Stanford Univ, Med Ctr, Dept Med, Div Bone Marrow Transplantat, Stanford, CA 94305 USA
关键词
autologous transplantation; T cells; immunotherapy; NK-T cells; cytotoxicity;
D O I
10.1053/bbmt.2001.v7.pm11349808
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Immunotherapy may potentially improve the outcome of autologous hematopoietic cell transplantation (HCT). Poor effector cell proliferation and marginal antitumor activity limit attempts to use immunotherapy. We have characterized the ex vivo expansion, up to 1000-fold, of CD3(+)CD56(+) lymphocytes from the peripheral blood lymphocytes (PBL) of healthy donors. Expanded cells termed cytokine-induced killer (CIK) cells induce non-major histocompatibility complex-restricted lysis of tumor cells and demonstrate cytolytic activity superior to lymphokine-activated killer cells without the requirement of interleukin (IL)-2 treatment in vivo. To determine whether cytolytic cells could be expanded from patient material, we evaluated samples of peripheral blood progenitor cells (PBPCs) from 25 patients undergoing autologous HCT. The PBPCs were expanded by priming with interferon-gamma followed by anti-CD3 monoclonal antibody and IL-2 the next day. Fluorescence-activated cell sorting analysis was performed on days 0, 15, 21, and 28 of cell culture. The median T-cell content rose from 15.3% (range, 1.1% to 89.7%) on day 0 to 97.2% (range, 83.6% to 99.5%) by day 15. By day 21, T cells expanded 21.8-fold (range, 1.7- to 420.0-fold) and CD3(+)CD56(+) cells expanded 44.8-fold (range, 5.1- to 747.0-fold). CIK cells were used as effector cells against B-cell lymphoma targets (OCI-Ly8) with a median of 24% (range, 3% to 67%) and 42% (range, 6% to 96%) specific lysis of target cells on days 21 and 28, respectively. CIK cells derived from PBL of 2 additional patients with acute myelogenous leukemia demonstrated 39% and 78% specific lysis of OCI-Ly8 and 26% and 58% specific lysis of autologous leukemic blasts at an effector:target ratio of 40:1. CIK cells may be expanded from granulocyte colony-stimulating factor-mobilized PBPCs of patients undergoing posttransplantation adoptive immunotherapy.
引用
收藏
页码:216 / 222
页数:7
相关论文
共 31 条
[1]   A prospective, randomized trial of autologous bone marrow transplantation and chemotherapy in multiple myeloma [J].
Attal, M ;
Harousseau, JL ;
Stoppa, AM ;
Sotto, JJ ;
Fuzibet, JG ;
Rossi, JF ;
Casassus, P ;
Maisonneuve, H ;
Facon, T ;
Ifrah, N ;
Payen, C ;
Bataille, R .
NEW ENGLAND JOURNAL OF MEDICINE, 1996, 335 (02) :91-97
[2]  
BENYUNES MC, 1995, BONE MARROW TRANSPL, V16, P283
[3]  
BOSLY A, 1992, EXP HEMATOL, V20, P962
[4]  
Champlin Richard, 1999, Current Opinion in Oncology, V11, P87
[5]   Donor leukocyte infusions in 140 patients with relapsed malignancy after allogeneic bone marrow transplantation [J].
Collins, RH ;
Shpilberg, O ;
Drobyski, WR ;
Porter, DL ;
Giralt, S ;
Champlin, R ;
Goodman, SA ;
Wolff, SN ;
Hu, W ;
Verfaillie, C ;
List, A ;
Dalton, W ;
Ognoskie, N ;
Chetrit, A ;
Antin, JH ;
Nemunaitis, J .
JOURNAL OF CLINICAL ONCOLOGY, 1997, 15 (02) :433-444
[6]   G-CSF-MOBILIZED PERIPHERAL-BLOOD PROGENITOR CELLS FOR ALLOGENEIC TRANSPLANTATION - SAFETY, KINETICS OF MOBILIZATION, AND COMPOSITION OF THE GRAFT [J].
DREGER, P ;
HAFERLACH, T ;
ECKSTEIN, V ;
JACOBS, S ;
SUTTORP, M ;
LOFFLER, H ;
MULLERRUCHHOLTZ, W ;
SCHMITZ, N .
BRITISH JOURNAL OF HAEMATOLOGY, 1994, 87 (03) :609-613
[7]   Immune reconstitution and immunotherapy after autologous hematopoietic stem cell transplantation [J].
Guillaume, T ;
Rubinstein, DB ;
Symann, M .
BLOOD, 1998, 92 (05) :1471-1490
[8]   Effect of filgrastim treatment on inflammatory cytokines and lymphocyte functions [J].
Hartung, T ;
Doecke, WD ;
Bundschuh, D ;
Foote, M ;
Gantner, F ;
Hermann, C ;
Lenz, A ;
Milwee, S ;
Rich, B ;
Simon, B ;
Volk, HD ;
von Aulock, S ;
Wendel, A .
CLINICAL PHARMACOLOGY & THERAPEUTICS, 1999, 66 (04) :415-424
[9]   Expansion of Philadelphia chromosome-negative CD3+CD56+ cytotoxic cells from chronic myeloid leukemia patients:: In vitro and in vivo efficacy in severe combined immunodeficiency disease mice [J].
Hoyle, C ;
Bangs, CD ;
Chang, P ;
Kamel, O ;
Mehta, B ;
Negrin, RS .
BLOOD, 1998, 92 (09) :3318-3327
[10]   Transplant-lite:: Induction of graft-versus-malignancy using fludarabine-based nonablative chemotherapy and allogeneic blood progenitor cell transplantation as treatment for lymphoid malignancies [J].
Khouri, IF ;
Keating, M ;
Körbling, M ;
Przepiorka, D ;
Anderlini, P ;
O'Brien, S ;
Giralt, S ;
Ippoliti, C ;
von Wolff, B ;
Gajewski, J ;
Donato, M ;
Claxton, D ;
Ueno, N ;
Andersson, B ;
Gee, A ;
Champlin, R .
JOURNAL OF CLINICAL ONCOLOGY, 1998, 16 (08) :2817-2824