Synergistic actions of picibanil (OK-432) on recombinant interleukin-2 induction of tumor-infiltrating lymphocyte expansion, cytotoxicity, and phenotypic differentiation.

R Lafreniere, K Borkenhagen, L D Bryant, E Ng, S Hayton
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Abstract

Tumor-infiltrating lymphocytes (TILs) comprise a subpopulation of lymphoid cells that infiltrate into growing tumors. These cells can be activated in vitro with recombinant interleukin-2 (rIL-2) to become highly cytotoxic against fresh tumor targets in vitro and against a variety of systemic metastases in vivo. OK-432 is a well-known inducer of NK cells and immune effector T cells. This study was designed to evaluate the effects of OK-432 on (a) the generation and (b) the cytotoxic potential of rIL-2-induced TILs. When TILs obtained from a murine colon adenocarcinoma (the MC-38 tumor) were cultured in complete media supplemented with 100 U of rIL-2/ml and 1.0 microgram of OK-432/ml, the number of TILs generated was greater than that seen with rIL-2 or OK-432 alone (number of TILs on day 15 of culture: 100 U of rIL-2/ml: 268 x 10(5) TILs; 1.0 microgram of OK-432/ml: 30 x 10(5) TILs; 100 U of rIL-2/ml + 1.0 microgram of OK-432/ml: 528 x 10(5) TILs). Higher concentrations of OK-432 had deleterious effects on TIL growth characteristics. TILs generated in 100 U of rIL-2 and 1.0 microgram of OK-432/ml of complete media demonstrated greater tumor lysis compared to rIL-2 alone (% lysis against MCA-102 target; 100 U of rIL-2/ml: 12%; 100 U of rIL-2/ml and 1.0 microgram of OK-432/ml: 50%; effector target ratio 20:1; p less than 0.001). Similar results were seen against the NK-sensitive YAC-1 lymphoma target.(ABSTRACT TRUNCATED AT 250 WORDS)

吡替尼(OK-432)对重组白细胞介素-2诱导肿瘤浸润淋巴细胞扩增、细胞毒性和表型分化的协同作用
肿瘤浸润淋巴细胞(肿瘤浸润淋巴细胞)由淋巴样细胞亚群组成,浸润到生长中的肿瘤中。这些细胞可以在体外被重组白细胞介素-2 (il -2)激活,在体外对新鲜肿瘤靶点和体内多种系统性转移具有高度的细胞毒性。OK-432是一种众所周知的NK细胞和免疫效应T细胞诱导剂。本研究旨在评估OK-432对il -2诱导的TILs的(a)产生和(b)细胞毒潜能的影响。从小鼠结肠腺癌(MC-38肿瘤)中获得的TILs在添加100 U rIL-2/ml和1.0微克OK-432/ml的完整培养基中培养时,产生的TILs数量大于单独使用rIL-2或OK-432(培养第15天的TILs数量:100 U rIL-2/ml: 268 × 10(5)个TILs;1.0微克OK-432/ml: 30 × 10(5) TILs;100u rIL-2/ml + 1.0微克OK-432/ml: 528 × 10(5) TILs)。较高浓度的OK-432对TIL生长特性有有害影响。与单独使用rIL-2相比,在100u rIL-2和1.0微克OK-432中产生的TILs显示出更大的肿瘤溶解(对MCA-102靶点的裂解%;il -2 100u /ml: 12%;il -2 100u /ml, OK-432 1.0微克/ml: 50%;效应靶比20:1;P < 0.001)。对nk敏感的YAC-1淋巴瘤靶标也有类似的结果。(摘要删节250字)
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