RETARDATION OF METASTATIC TUMOR-GROWTH AFTER IMMUNIZATION WITH METASTASIS-SPECIFIC MONOCLONAL-ANTIBODIES

被引:82
作者
REBER, S
MATZKU, S
GUNTHERT, U
PONTA, H
HERRLICH, P
ZOLLER, M
机构
[1] GERMAN CANC RES CTR,INST RADIOL & PATHOPHYSIOL,NEUENHEIMER FELD 280,W-6900 HEIDELBERG 1,GERMANY
[2] UNIV KARLSRUHE,INST GENET,W-7500 KARLSRUHE,GERMANY
[3] KERNFORSCHUNGSZENTRUM KARLSRUHE GMBH,INST GENET & TOXICOL,W-7500 KARLSRUHE 1,GERMANY
关键词
D O I
10.1002/ijc.2910460528
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
The influence of 4 murine monoclonal antibodies (MAbs) directed against surface determinants of a metastasizing rat adenocarcinoma (BSp73ASML) on metastatic spread was evaluated and compared to their in vivo binding as well as to the induction of a humoral anti‐MAb response, especially with respect to the development of anti‐idiotypic (ID) antibodies of the internal image type. In a protocol of explicit immunization, all 4 MAbs transiently inhibited metastatic growth. Survival was prolonged only with one MAb (4.4ASML). With another MAb (1.1ASML), directed against a new variant form of CD44, metastatic growth was accelerated after transient retardation. Retardation of metastatic growth correlated with the humoral anti‐MAb response. This accounted for the isotype‐ as well as for the idiotype‐specific response. An exception was noted after immunization with MAb 1.1ASML. Rats with high levels of anti‐1.1ASML antibodies, which inhibited binding to the tumor cells (internal image‐type antibodies) showed accelerated metastatic spread. Data are interpreted to mean that MAb‐induced inhibition of metastatic spread may be based on 2 independent mechanisms: blockade of metastasis‐associated epitopes (i. e., with MAb 1.1ASML) and induction of an anti‐mouse lg response. In the latter case it was irrelevant whether the response was isotype‐ or idiotype‐specific. Copyright © 1990 Wiley‐Liss, Inc., A Wiley Company
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页码:919 / 927
页数:9
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共 65 条
[1]  
Badger C.C., Bernstein I.D., Prospects for monoclonal antibody therapy of leukemia and lymphoma, Cancer, 58, pp. 584-589, (1986)
[2]  
Badger C.C., Shulman H., Peterson A.V., Bernstein I.D., Monoclonal antibody therapy of spontaneous AKR T cell leukemia, Cancer Res., 46, pp. 4058-4063, (1986)
[3]  
Barth A., Waibel R., Stahel R.A., Monoclonal anti‐idiotypic antibody mimicking a tumor‐associated sialogycoprotein antigen induces humoral immune response against human small‐cell lung carcinoma, Int. J. Cancer, 43, pp. 896-900, (1989)
[4]  
Basham T.Y., Palladino M.A., Badger C.C., Bernstein I.D., Levy R., Merigan T.C., Comparison of combinations of interferons with tumor‐specific and nonspecific monoclonal antibodies as therapy for murine B‐ and T‐cell lymphomas, Cancer Res., 48, pp. 4196-4200, (1988)
[5]  
Bennet B., Isolation and cultivation in vitro of macrophages from various sources in the mouse, Amer. J. Path., 48, pp. 165-172, (1966)
[6]  
Bhattacharya-Chatterjee M., Chatterjee S.K., Vasile S., Seon B.K., Kohler H., Idiotype vaccines against human T cell leukemia. II. Generation and characterization of a monoclonal idiotype cascade (Ab1, Ab2 and Ab3), J. Immunol., 141, pp. 1398-1403, (1988)
[7]  
Bhattacharya-Chatterjee M., Pride M.W., Seon B.K., Kohler H., Idiotype vaccines against human T cell acute lymphoblastic leukemia. I. Generation and characterization of biologically active monoclonal anti‐idiotopes, J. Immunol., 139, pp. 1354-1360, (1987)
[8]  
Carrasquillo J.A., Krohn K.A., Beaumier P., McGuffin R.W., Brown J.P., Hellstrom K.E., Hellstrom J., Larson S.M., Diagnosis and therapy for solid tumors with radiolabeled antibodies and immune fragments, Cancer Treat. Rep., 68, pp. 317-328, (1984)
[9]  
Ciavarra R.P., Vitetta E.S., Forman J., Growth inhibition of a B cell leukemia: evidence implicating an anti‐idiotype immune response for protective immunity, J. Immunol., 137, pp. 1371-1375, (1986)
[10]  
Clark M.R., Waldmann H., T cell killing of target cells induced by hybrid antibodies: comparison of two bispecific monoclonal antibodies, J. nat. Cancer Inst., 79, pp. 1393-1401, (1987)