Dendritic cells pulsed with apoptotic squamous cell carcinoma have anti-tumor effects when combined with interleukin-2

被引:14
作者
Son, YI
Mailliard, RB
Watkins, SC
Lotze, MT
机构
[1] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Dept Otolaryngol,Kangnam Ku, Seoul 135710, South Korea
[2] Univ Pittsburgh, Sch Med, Dept Surg, Pittsburgh, PA 15261 USA
[3] Univ Pittsburgh, Sch Med, Dept Cell Biol & Physiol, Pittsburgh, PA 15261 USA
关键词
immunotherapy; dendritic cells; apoptosis; interleukin-2; squamous cell carcinoma;
D O I
10.1097/00005537-200108000-00026
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Objectives: Dendritic cells, the most potent of the antigen presenting cells, have been widely studied as a promising tool for antitumor immunotherapies. However, little has been determined about the efficacy of dendritic cell-based therapy for the treatment of squamous cell carcinoma (SCC) because there are no known SCC-specific antigens. Recent reports indicate that dendritic cells can acquire antigens in the form of apoptotic cells and induce cytotoxic T-lymphocyte responses. The aim of this study was to test the feasibility of adoptive dendritic cell immunotherapy against SCC by using apoptotic tumor cells as a source of tumor antigens. Study Design: A poorly immunogenic SCC line KLN 205 was used to make subcutaneous tumors on the flank of DBA2/J syngeneic mice. Bone marrow-derived dendritic cells were pulsed with ultraviolet B-irradiated (apoptotic) KLN 205 cells in vitro and transferred to the opposite flank subcutaneously. Some of the animals received simultaneous intraperitoneal injections of low-dose interleukin-2. Results. When combined with interleukin-2, adoptive transfers of dendritic cells that were pulsed with apoptotic SCC significantly suppressed the tumor growth (P < .001) without notable side effects. Splenic T cells of treated mice produced greater amounts of interferon-gamma when restimulated. with the relevant tumor (P < .001) as compared with control groups, indicative of an effective T-cell-mediated systemic immune response. Conclusion: Adoptive transfer of dendritic cells pulsed with apoptotic tumor cells as a source of tumor antigens, can elicit effective antitumor responses in the poorly immunogenic SCC model when combined with interleukin-2.
引用
收藏
页码:1472 / 1478
页数:7
相关论文
共 28 条
[1]   PHOTOTHERAPY [J].
ABEL, EA .
DERMATOLOGIC CLINICS, 1995, 13 (04) :841-&
[2]   Dendritic cells acquire antigen from apoptotic cells and induce class I restricted CTLs [J].
Albert, ML ;
Sauter, B ;
Bhardwaj, N .
NATURE, 1998, 392 (6671) :86-89
[3]  
Atkins MB, 2000, CANCER J SCI AM, V6, pS11
[4]   Dendritic cells and the control of immunity [J].
Banchereau, J ;
Steinman, RM .
NATURE, 1998, 392 (6673) :245-252
[5]   REEVALUATION OF THE SUPERIORITY OF POLYETHYLENE GLYCOL-MODIFIED INTERLEUKIN-2 OVER REGULAR RECOMBINANT INTERLEUKIN-2 [J].
BERNSEN, MR ;
DULLENS, HFJ ;
DENOTTER, W ;
HEINTZ, APM .
JOURNAL OF INTERFERON AND CYTOKINE RESEARCH, 1995, 15 (07) :641-645
[6]   Peptide-pulsed dendritic cells induce antigen-specific, CTL-mediated protective tumor immunity [J].
Celluzzi, CM ;
Mayordomo, JI ;
Storkus, WJ ;
Lotze, MT ;
Falo, LD .
JOURNAL OF EXPERIMENTAL MEDICINE, 1996, 183 (01) :283-287
[7]  
Curiel-Lewandrowski C, 1999, J IMMUNOL, V163, P174
[8]  
Dutcher JP, 1997, CANCER J, V3, pS73
[9]   ANTIGENIC-STIMULATION REGULATES THE LEVEL OF EXPRESSION OF INTERLEUKIN-2 RECEPTOR ON HUMAN T-CELLS [J].
HEMLER, ME ;
BRENNER, MB ;
MCLEAN, JM ;
STROMINGER, JL .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES, 1984, 81 (07) :2172-2175
[10]  
HOCKENBERY D, 1995, AM J PATHOL, V146, P16