[Design and synthesis of conjugates between antineoplastic agents and monoclonal antibodies].

Abstract

The production of conjugates between anti-tumor agents and monoclonal antibodies in order to achieve a more selective therapy of cancer has been a research field in continuous expansion during the last years. The present study is directed towards trying to define a practice guide to be used in the design and synthesis of this type of conjugates. The points considered refer to the characteristics which have to be taken into account of each of the parts which constitute the conjugate (monoclonal antibody or fragments and the anti-tumor agent) and also of the method of synthesis, according to our experience and experience gained in other laboratories. The qualities studied of the antibody are its specificity towards tumour cells, intrinsic cytotoxicity, molecular size, antigenicity, resistance to manipulation, biological half life and antigenic modulation properties. Referent to the cytotoxic agent the properties to deal with are its toxicity, presence of functional groups, hydrophobicity, ionic charge, unspecific interaction sites, molecular weight, resistance to manipulation and antigenicity. The characteristics to take into account of the method of synthesis are its simplicity, the homogeneity of the products obtained, the difficulty in purifying the products, the smoothness of the reaction and the type of conjugate formed (that is, whether the agent has been directly linked to the antibody or linked to it via a "bridge" molecule). The ideal characteristics referring to every one of these points have been selected having in mind the possibility of clinical application of this type of conjugates that we expect to have a specific cytotoxic action on tumour cells once the antibody has been selectively localized in the tumour and has targeted there the cytotoxic agent coupled to it. Some of the points studied are, however, still open to further evaluation.