BISPECIFIC MONOCLONAL-ANTIBODY ANTI-CD3-X-ANTI-TENASCIN - AN IMMUNOTHERAPEUTIC AGENT FOR HUMAN GLIOMA

被引:26
作者
BONINO, LD
DEMONTE, LB
SPAGNOLI, GC
VOLA, R
MARIANI, M
BARONE, D
MORO, AM
RIVA, P
NICOTRA, MR
NATALI, PG
MALAVASI, F
机构
[1] UNIV TURIN,DIPARTIMENTO GENET BIOL & CHIM MED,CELL BIOL LAB,I-10126 TURIN,ITALY
[2] CNR,CIOS,I-10126 TURIN,ITALY
[3] UNIV BASEL,DEPT SURG,CH-4031 BASEL,SWITZERLAND
[4] UNIV BASEL,DEPT RES,CH-4031 BASEL,SWITZERLAND
[5] SORIN BIOMED SPA,I-13040 SALUGGIA,ITALY
[6] IST RBM A MARXER,I-10015 IVREA,ITALY
[7] INST BUTANTAN,CTR BIOTECHNOL,BR-05503900 SAO PAULO,BRAZIL
[8] HOSP M BUFALINI,DEPT NUCL MED,I-47023 CESENA,ITALY
[9] CNR,IST TECNOL BIOMED,I-00100 ROME,ITALY
[10] IST TUMORI REGINA ELENA,IMMUNOL LAB,I-00100 ROME,ITALY
[11] UNIV ANCONA,IST BIOL & GENET,ANCONA,ITALY
关键词
D O I
10.1002/ijc.2910610414
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Besides surgery, the therapeutic possibilities for the treatment of human gliomas include adoptive cellular immunotherapy, radioimmunotherapy, immunotherapy mediated by chemoimmunoconjugates and, more recently, bispecific monoclonal antibodies (biMAbs). Anti-CD3 x anti-tenascin (TN) is the first reagent of a number of biMAbs under investigation for prospective use in vivo to maximize the cell-mediated cytolytic potential of glioma patients. This biMAb originated from the fusion of 2 parental hybridomas, made resistant by retrovirus-mediated infection to the different metabolic drugs, geneticin and methotrexate, respectively. The resulting hybrid hybridomas were selected on the basis of the double specificity for CD3 and TN, cloned several times and grown under continuous metabolic pressure. The different families of recombinant antibodies were then purified by high-pressure liquid chromatography on hydroxylapatite columns. Immunohistochemical studies on tumor specimens of different origin and histotype have shown that the selected biMAb presented a distribution pattern similar to that of the parental anti-TN MAb, maintaining the same staining homogeneity and intensity. Moreover, the mitogenic activity of anti-CD3 x anti-TN biMAb on peripheral blood mononuclear cells was similar to that featured by the parental anti-CD3 MAb. Furthermore, the hybrid molecule induced TNF-alpha gene expression in activated PBMC. Finally, the anti-CD3 x anti-TN featured the desired killer targeting ability, being able to induce a significantly increased cytotoxic activity against TN+ tumor cells. (C) 1995 Wiley-Liss, Inc.
引用
收藏
页码:509 / 515
页数:7
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