The clinical significance of HAMA in patients treated with mouse monoclonal antibodies.
Twenty-four patients were analyzed for the development of HAMA (human antimouse antibodies) after being treated with repeated doses (200-500 mg) of the mouse monoclonal antibody (MAb) 17-1A. All patients developed anti-17-1A IgG antibodies, and most of them also developed IgM antibodies. In only two patients could immune complexes be demonstrated. Allergic reactions were rare (1.9%). In an extended study, a further 19 patient were analyzed for an idiotypic response. Forty-one out of 43 patients developed antiidiotypic antibodies (ab2), and 20 of these also anti-anti-idiotypic antibodies (ab3). Ab3+ patients responded significantly better (p = 0.01) and survived longer (p < 0.001) compared to ab3- patients. In this study, we showed that MAb 17-1A could be repeatedly given on a safe basis. The development of high titers of HAMA did not cause significant clinical problems when further repeated infusions of MAb 17-1A were given. The development of an idiotypic response also indicate that the induction of HAMA might be beneficial and not harmful to the patient.
Frödin
J E
JE
Department of Oncology (Radiumhemmet), Karolinska Hospital, Stockholm, Sweden.
Lefvert
A K
AK
Mellstedt
H
H
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D015179:Colorectal Neoplasms / Q000401:mortality / Q000503:physiopathology / Q000628:therapy; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007167:Immunotherapy / Q000592:standards; D008297:Male; D051379:Mice / Q000276:immunology*; D008875:Middle Aged
D000911:Antibodies, Monoclonal