Human anti-mouse antibody response to the injection of murine monoclonal antibodies against IL-6

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Abstract
We analysed human anti‐mouse antibodies (HAMA) in 12 patients (six with multiple myeloma (MM) and six with metastatic renal cell carcinoma (MRCC)) who were treated with B‐E8, an IgG1 MoAb against IL‐6. Efficiency of the treatment was evidenced by the drop in the serum levels of C‐reactive protein (CRP), the in vivo production of which is under the control of IL‐6. Three patients with MM and the six patients with MRCC became immunized m the injected MoAb. HAMA appeared between days 7 and 15 after the beginning of the treatment. The nine patients made IgG antibodies: four also made IgM. All immunized patients made anti‐biotype antibodies specific to B‐E8. Two of them also developed HAMA directed to murine IgG1 isotype: in these two patients B‐E8 MoAb cleared rapidly from the circulation with loss of treatment efficiency. In the patients who developed only anti‐biotype antibodies, serum levels of B‐E8 remained unchanged and CRP production remained inhibited, indicating that treatment remained efficient in the presence of HAMA, Circulating B‐E8 MoAbs were still able to bind to iL‐6 and to inhibit IL‐6‐dependent proliferation despite the presence of anti‐idiotypic HAMA, Therefore, in contrast to HAMA produced against MoAb directed against cellular targets, HAMA against anti‐IL‐6 MoAb idiotopes led neither to clearance nor to functional inactivation of the injected MoAb. This was further shown by resuming the B‐E8 treatment with success in a patient who still had anti‐idiotypic HAMA.