POTENTIAL TO INVOLVE MULTIPLE EFFECTOR-CELLS WITH HUMAN RECOMBINANT INTERLEUKIN-2 AND ANTIGANGLIOSIDE MONOCLONAL-ANTIBODIES IN A CANINE MALIGNANT-MELANOMA IMMUNOTHERAPY MODEL
POTENTIAL TO INVOLVE MULTIPLE EFFECTOR-CELLS WITH HUMAN RECOMBINANT INTERLEUKIN-2 AND ANTIGANGLIOSIDE MONOCLONAL-ANTIBODIES IN A CANINE MALIGNANT-MELANOMA IMMUNOTHERAPY MODEL
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DOI：
10.1097/00002371-199410000-00003
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发表时间：
1994-10-01
影响因子：
3.9
通讯作者：
SONDEL, PM
中科院分区：
文献类型：
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作者：
HELFAND, SC;SOERGEL, SA;SONDEL, PM
源自神经外胚层细胞的人类肿瘤，如恶性黑素瘤和神经母细胞瘤，表达高水平的二唾液酸神经节苷脂GD 2和GD 3，使这些抗原成为单克隆抗体（Mab）靶向的理想抗原。本研究的目的是研究神经节苷脂在犬黑色素瘤中的表达和靶向性。使用免疫组织化学方法，我们分析了双唾液酸神经节苷脂GD 2和GD 3在犬口腔恶性黑色素瘤中的表达，小鼠单克隆抗体14.G2a和R24分别识别人肿瘤上的GD 2和GD 3双唾液酸神经节苷脂。我们还评估了Mab 14.G2a（及其小鼠-人嵌合体，ch 14.18）在体外用人重组白细胞介素-2（IL-2）激活的犬外周血淋巴细胞（PBL）或犬中性粒细胞效应细胞介导针对犬恶性黑素瘤细胞系的抗体依赖性细胞毒性（ADCC）的能力。我们的数据显示，Mab 14.G2a和R24识别新鲜冷冻的犬口腔黑素瘤。Mab 14.G2a或ch 14.18或IL-2通过犬PBL增强犬恶性黑素瘤细胞系的裂解。使用Mab与IL-2的组合观察到的杀伤作用是相加的。Mab 14.G2a通过犬中性粒细胞介导犬黑素瘤的有效ADCC。这些研究表明，二唾液酸神经节苷脂表达新鲜的犬黑色素瘤细胞。与这些抗原反应的单克隆抗体可以靶向并触发多种犬效应群体的肿瘤杀伤，IL-2可以通过犬淋巴细胞增强这些作用。因此，犬口腔恶性黑色素瘤（犬中自发发生的转移性癌症）可能是研究使用抗肿瘤单抗和IL-2进行联合免疫治疗的相关动物模型。
Human tumors originating from neuroectodermal cells such as malignant melanoma and neuroblastoma express high levels of disialogangliosides GD2 and GD3, making these antigens ideal for targeting by monoclonal antibodies (Mabs). The purpose of this study was to investigate expression and targeting of gangliosides on canine melanoma. Using immunohistochemical methods, we analyzed the expression of disialogangliosides GD2 and GD3 on canine oral malignant melanomas with murine Mabs 14.G2a and R24 that recognize GD2 and GD3 disialogangliosides, respectively, on human tumors. We also assessed the ability of Mab 14.G2a (and its mouse-human chimera, ch 14.18) to mediate antibody-dependent cellular cytotoxicity (ADCC) in vitro against a canine malignant melanoma cell line with human recombinant interleukin-2 (IL-2) activated canine peripheral blood lymphocytes (PBL), or canine neutrophil effector cells. Our data show that Mabs 14.G2a and R24 recognized fresh frozen canine oral melanoma. Mabs 14.G2a or ch 14.18, or IL-2, potentiated lysis of the canine malignant melanoma cell line by canine PBL. The killing effect observed using the combination of either Mab with IL-2 was additive. Mab 14.G2a mediated potent ADCC of canine melanoma by canine neutrophils. These studies indicate that disialogangliosides are expressed on fresh canine melanoma cells. Mabs reactive with these antigens can target and trigger tumor killing by multiple canine effector populations and IL-2 can potentiate these effects by canine lymphocytes. Thus, canine oral malignant melanoma, a spontaneously occurring, metastatic cancer in the dog, may be a relevant animal model to investigate combination immunotherapy using antitumor Mab and IL-2.