Treatment of pathologies which escape the immune response, using optimised antibodies
The invention relates to the use of optimised human or humanised chimeric monoclonal antibodies which are produced cell lines, said antibodies having a strong affinity for receptor CD16 of the effector cells of the immune system and being able to induce the secretion of cytokines and interleukins, in particular 1′ IFN? or 1′ IL2, for the treatment of pathologies for which the target cells only express a low antigenic density and in which the effector cells can only be recruited in small quantities.
1 . The use of an optimized human or humanized chimeric monoclonal antibody, characterized in that:
a) it is produced in a cell line selected for its properties of glycosylation of the Fc fragment of an antibody, or
b) the glycan structure of the Fcgamma has been modified ex vivo, and/or
c) its primary sequence has been modified so as to increase its reactivity with respect to Fc receptors; said antibody having i) a rate of FcγRIII (CD16)-dependant ADCC of greater than 50%, preferably greater than 100%, for an E/T (effector cell/target cell) ratio of less than 5/1, preferably less than 2/1, compared with the same antibody produced in a CHO line; and ii) a rate of production of at least one cytokine by a Jurkat CD 16 effector cell or by a CD 16 receptor-expressing effector cell of the immune system of greater than 50%, 100%, or preferably greater than 200%, compared with the same antibody produced in a CHO line; for preparing a medicinal product intended for the treatment of pathologies for which the number of antigenic sites or the antigenic density is low, or the antigens are relatively inaccessible to antibodies, or else for which the number of activated or recruited effector cells is low.
2 . The use as claimed in claim 1 , characterized in that the number of antigenic sites is less than 250 000, preferably less than 100 000 or 50 000 per target cell.
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