Antibody-dependent cell-mediated cytotoxicity induced by active immunotherapy based on racotumomab in non-small cell lung cancer patients

被引:18
作者
Segatori, Valeria I. [1 ]
Cuello, Hector A. [1 ]
Gulino, Cynthia A. [1 ]
Alberto, Marina [1 ]
Venier, Cecilia [2 ]
Guthmann, Marcelo D. [3 ]
Demarco, Ignacio A. [3 ]
Alonso, Daniel F. [1 ]
Gabri, Mariano R. [1 ]
机构
[1] Natl Univ Quilmes, Mol Oncol Lab, Roque Saenz Pena 352,B1876BXD, Bernal, Argentina
[2] Univ Buenos Aires, Inst Immunol Genet & Metab INIGEM, Ave Cordoba 2351,C1120AAF, Buenos Aires, DF, Argentina
[3] Elea Labs, Sanabria 2353,C1417AZE, Buenos Aires, DF, Argentina
关键词
Racotumomab; Active immunotherapy; ADCC; Non-small cell lung cancer; NeuGcGM3; ganglioside; N-GLYCOLYLNEURAMINIC ACID; NONHUMAN SIALIC-ACID; 1E10 ANTIIDIOTYPE VACCINE; GLYCOLYL GM3 GANGLIOSIDE; MONOCLONAL-ANTIBODIES; PROSTATE-CANCER; RECEPTOR; BREAST; EXPRESSION; EFFECTOR;
D O I
10.1007/s00262-018-2188-y
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Antitumor strategies based on positive modulation of the immune system currently represent therapeutic options with prominent acceptance for cancer patients' treatment due to its selectivity and higher tolerance compared to chemotherapy. Racotumomab is an anti-idiotype (anti-Id) monoclonal antibody (mAb) directed to NeuGc-containing gangliosides such as NeuGcGM3, a widely reported tumor-specific neoantigen in many human cancers. Racotumomab has been approved in Latin American countries as an active immunotherapy for advanced non-small cell lung cancer (NSCLC) treatment. In this work, we evaluated the induction of Ab-dependent cell-mediated cytotoxicity (ADCC) in NSCLC patients included in a phase III clinical trial, in response to vaccination with racotumomab. The development of anti-NeuGcGM3 antibodies (Abs) in serum samples of immunized patients was first evaluated using the NeuGcGM3-expressing X63 cells, showing that racotumomab vaccination developed antigen-specific Abs that are able to recognize NeuGcGM3 expressed in tumor cell membranes. ADCC response against NeuGcGM3-expressing X63 (target) was observed in racotumomab-treated- but not in control group patients. When target cells were depleted of gangliosides by treatment with a glucosylceramide synthase inhibitor, we observed a significant reduction of the ADCC activity developed by sera from racotumomab-vaccinated patients, suggesting a target-specific response. Our data demonstrate that anti-NeuGcGM3 Abs induced by racotumomab vaccination are able to mediate an antigen-specific ADCC response against tumor cells in NSCLC patients.
引用
收藏
页码:1285 / 1296
页数:12
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