Method for obtaining modified immunoglobulins with reduced immunogenicity of murine antibody variable domains, compositions containing them

摘要

Modified chimaeric antibodies, and antibody heavy and light chains, which comprise variable domains derived from a first mammalian species, usually mouse, and constant domains from a second mammalian species, usually human. Modification concerns the variable domains, in particular the framework regions of the variable domains. The modifications are made only in T-cell antigenic structures present in framework regions, and do not cover canonical structures or Vernier zone. The modifications adapt the amino acid sequences concerned to those occurring in corresponding antibodies derived from said second mammalian species. Thus, the modified chimaeric antibodies retain the original antigen recognition and binding properties but become less immunogenic to said second mammalian species, which improves their therapeutical utility with said second mammalian species. Recombinant DNA technology may be used to construct and produce the modified chimaeric antibodies.