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Humanized AntibodiesUnfortunately, some chimeric molecules are still able to induce a humoral immune response when administered to humans. Important Human Anti-Chimeric Antibody (HACA) responses have been found in 40% of the products used in humans . Efforts to reduce the immunogenicity of antibodies led to the creation, between 1988 and 1991, of “humanized” antibodies. This technology includes a variety of procedures, such as CDR grafting, Ab reshaping, and Ab resurfacing/veneering [33–35], based on the substitution of the residues of the anchor domains or “Framework” of the murine variable region by human sequences, until only the three hypervariable regions (5–10% of the sequence) are of murine origin and all the rest of human origin .
Dosage of ACTH was tapered by 87 %. Reduction in total CSF B cells was profound at 6 months (-93 %). By study end, peripheral B cells returned to 53 % of baseline and serum IgM levels to 63 %. Overall clinical response trailed peripheral B cell and IgM depletion, but improvement continued after their levels recovered. All but 1 non-ambulatory subject became ambulatory without additional chemotherapy; 2 relapsed and remitted; 4 had rituximab-related or possibly related adverse events; and 2 had low-titer human anti-chimeric antibody.
The presence of this murine component provides a source of potential immunogenicity for humans. In facts, chimeric antibodies, such as IFX, can induce strong human anti-chimeric antibody.
2010). Given this limitation in interpreting the immunogenicity data, it is generally accepted that infliximab, a mouse-human chimeric antibody with human constant regions (~75% of the immunoglobulin sequence) and mouse variable regions (~25% of the sequence), is more immunogenic than humanized or human antibody agents such as adalimumab, golimumab, and certolizumab pegol ( Yoon et al. , 2010). The incidence of human anti-chimeric antibody.