REACTIVATION OF MURINE TUMOR-INFILTRATING LYMPHOCYTES WITH SOLID-PHASE ANTI-CD3 ANTIBODY - IN-VITRO CYTOKINE PRODUCTION IS ASSOCIATED WITH IN-VIVO EFFICACY

被引：34

作者：

GOEDEGEBUURE, PS ^{[1
]}

ZUBER, M ^{[1
]}

LEONARDVIDAL, DL ^{[1
]}

BURGER, UL ^{[1
]}

CUSACK, JC ^{[1
]}

CHANG, MP ^{[1
]}

DOUVILLE, LM ^{[1
]}

EBERLEIN, TJ ^{[1
]}

机构：

[1] HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DEPT SURG,DIV SURG ONCOL,75 FRANCIS ST,BOSTON,MA 02115

来源：

SURGICAL ONCOLOGY-OXFORD | 1994年 / 3卷 / 02期

关键词：

ANTI-CD3; CYTOKINES; MONOCLONAL ANTIBODY; MURINE; REACTIVATION; TUMOR-INFILTRATING LYMPHOCYTES;

D O I：

10.1016/0960-7404(94)90003-5

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Previously we described the use of solid-phase anti-CD3 monoclonal antibody (mAb) to stimulate murine tumour-infiltrating lymphocytes (TIL) and their subsequent expansion in recombinant interleukin 2 (rIL-2). In a pulmonary metastases model using the methylcholanthrene-induced sarcoma MCA-105 anti-CD3 activated TIL were capable of eradicating disease similar to TIL cultured in rIL-2 only. Here we extend these observations by characterizing the biological effects of sequential solid-phase anti-CD3 activation. TIL from MCA-105 tumour activated with solid-phase anti-CD3 on day 1 were reactivated on day 14, or day 26, or both and compared to TIL grown in rIL-2 only or TIL activated with anti-CD3 once on day 1. Reactivation enhanced in vitro proliferation 1.8- to 4-fold compared to TIL activated once with anti-CD3 (P < 0.05). In addition, the total lytic capacity of the cultures was enhanced after reactivation without changing the phenotype of the TIL cultures. Reactivation resulted in a greater in vivo efficacy when the TIL were administered within 72 h of reactivation. In contrast, TIL activated with anti-CD3 on day 1 and day 14 were least effective of all TIL cultures (P < 0.05). This correlated with in vitro cytokine production. The most effective TIL cultures in vivo produced 4- to 100-fold higher amounts of cytokines, especially interferon gamma (IFNgamma) and granulocyte macrophage colony stimulating factor (GM-CSF), than the other cultures. On the other hand, the least effective in vivo TIL culture, TIL activated with anti-CD3 on day 1 and 14, produced little or no cytokines. These data suggest that in vitro production of cytokines is indicative of in vivo efficacy of anti-CD3 activated TIL.

引用

页码：79 / 89

页数：11

共 40 条

[1] Rosenberg, Terry, Passive immunotherapy of cancer in animals and man, Adv Cancer Res, 25, pp. 323-328, (1977)
[2] Smith, Harmel, Hanna, Zwelling, Zbar, Rapp, Regression of established intradermal tumours and lymph node metastases in guinea pig after systemic transfer of immune lymphoid cells, J Natl Cancer Inst, 58, pp. 1315-1322, (1977)
[3] Fernandez-Cruz, Halliburton, Feldman, In vivo elimination by specific effectors of an established syngeneic rat Moloney virus-induced sarcoma, J Immunonl, 123, pp. 1772-1777, (1979)
[4] Eberlein, Rosenstein, Spiess, Wesley, Rosenberg, Adoptive chemoimmunotherapy of syngeneic murine lymphoma using long-term lymphoid cell lines expanded in T cell growth factor, Cancer Immunol Immunother, 13, pp. 5-13, (1982)
[5] Eberlein, Rosenstein, Rosenberg, Regression of a disseminated syngeneic solid tumour by systemic transfer of lymphoid cells expanded in interleukin-2, J Exp Med, 156, pp. 385-397, (1982)
[6] Mule, Shu, Schwarz, Rosenberg, Adoptive immunotherapy of established pulmonary metastases with LAK cells and recombinant interleukin-2, Science, 225, pp. 1487-1489, (1984)
[7] Mule, Shu, Rosenberg, The antitumour efficacy of lymphokine-activated killer cells and recombinant interleukin-2 in vivo, J Immunol, 135, pp. 646-652, (1985)
[8] Lafreniere, Rosenberg, Successful immuno-therapy of murine experimental hepatic metastases with lymphokine-activated killer cells and recombinant interleukin-2, Cancer Res, 45, pp. 3737-3741, (1985)
[9] Rosenberg, Spiess, Lafreniere, A new approach to the adoptive immunotherapy of cancer with tumour-infiltrating lymphocytes, Science, 233, pp. 1318-1321, (1986)
[10] Shu, Chou, Rosenberg, in vitro differentiation of T cells capable of mediating the regression of established syngeneic tumours in mice, Cancer Res, 47, pp. 1354-1360, (1986)

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