Human monoclonal anti-idiotypic antibodies. I. Establishment of immortalized cell lines from a tumor patient treated with mouse monoclonal antibodies.
Patients who undergo immunotherapy with a murine anti-colon carcinoma mAb (mAb17-1A) generate high titers of anti-idiotype and anti-isotype antibodies. Specifically selected anti-idiotypic antibodies that elicit in vivo a humoral and a cellular immune response against the nominal Ag can be used as surrogate Ag for immunization. We established from the B lymphocytes of a treated patient a series of EBV-transformed cell lines. Three weeks after immortalization, the cells were selected for production of antibodies (Ab2) against the Fab fragment of the murine mAb17-1A. The selected cells were cloned and screened by ELISA for specific anti-mAb17-1A idiotypic antibodies. Thirty-six out of 89 clones were anti-idiotypes. Cell culture supernatants and the purified Ig derived from 10 clones completely inhibited the specific binding of radiolabeled mAb17-1A to HT-29 colon carcinoma cells thus resembling Ab2-gamma anti-idiotypes. These cell lines which grow now in culture for 18 mo, continuously secrete IgG,K anti-Ab1-idiotype mAb. Human anti-idiotypic mAb might be candidates for vaccines when the nominal Ag itself is not available or cannot be used as such.
Steinitz
M
M
Department of Pathology, Hebrew University, Jerusalem, Israel.
Tamir
S
S
Frödin
J E
JE
Lefvert
A K
AK
Mellstedt
H
H
D000230:Adenocarcinoma / Q000276:immunology / Q000473:pathology* / Q000628:therapy; D000368:Aged; D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000096:biosynthesis* / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000096:biosynthesis* / Q000627:therapeutic use; D000918:Antibody Specificity; D002461:Cell Line, Transformed; D002472:Cell Transformation, Viral; D002999:Clone Cells / Q000378:metabolism / Q000473:pathology; D005260:Female; D004854:Herpesvirus 4, Human; D006801:Humans; D007074:Immunoglobulin G; D007130:Immunoglobulin Idiotypes / Q000276:immunology*; D008213:Lymphocyte Activation; D051379:Mice; D012811:Sigmoid Neoplasms / Q000276:immunology / Q000473:pathology* / Q000628:therapy
D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D007074:Immunoglobulin G; D007130:Immunoglobulin Idiotypes