Retardation of metastatic tumor growth after immunization with metastasis-specific monoclonal antibodies.
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 Ig response. In the latter case it was irrelevant whether the response was isotype- or idiotype-specific.
Reber
S
S
Institute of Radiology and Pathophysiology, German Cancer Research Center, Heidelberg.
Matzku
S
S
Günthert
U
U
Ponta
H
H
Herrlich
P
P
Zöller
M
M
D000230:Adenocarcinoma / Q000473:pathology / Q000556:secondary / Q000628:therapy*; D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use*; D000917:Antibody Formation / Q000276:immunology; D000918:Antibody Specificity; D000920:Antibody-Dependent Cell Cytotoxicity / Q000276:immunology; D007114:Immunization; D007074:Immunoglobulin G / Q000276:immunology; D007167:Immunotherapy; D051379:Mice; D009362:Neoplasm Metastasis / Q000276:immunology* / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000473:pathology / Q000556:secondary / Q000628:therapy; D051381:Rats; D011919:Rats, Inbred Strains
D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D007074:Immunoglobulin G; C048844:anti-IgG