The clinical significance of HAMA in patients treated with mouse monoclonal antibodies. |
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Authors: | J E Fr?din A K Lefvert H Mellstedt |
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Affiliation: | Department of Oncology (Radiumhemmet), Karolinska Hospital, Stockholm, Sweden. |
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Abstract: | 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. |
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