Immunotargeting of tumors: state of the art and prospects in 2000

Following 15 years of experimental studies, tumor immunotargeting using mon oclonal antibodies directed against tumor associated antigens shows now imp ortant clinical developments. This is mainly due to encouraging therapeutic results which have been obtained using humanized antibodies such as the an ti-CD20 rituximab in follicular B lymphomas and the anti-ErbB2 herceptin in breast carcinomas. Thanks to genetic engineering, it is possible to graft variable or hypervariable regions from murine antibodies to human IgG, and even to obtain fully human antibodies by using either transgenic mice conta ining a large part of the human repertoire of human IgG, or selection of hu man antibody fragments expressed by phages. Radiolabeling of antibodies pla yed a major role to demonstrate the tumor immunotargeting specificity and r emains attractive for the diagnosis by immunoscintigraphy as well as for th e treatment by radioimmunotherapy of some cancers. In this review, the curr ent results and the prospects of diagnostic and therapeutic uses of anti-tu mor antibodies and their fragments will be described. Concerning diagnosis, 123-iodine or 99m-technetium labeled Fab fragments allowed very demonstrat ive tumor images but this technique has a limited effect upon the therapeut ic attitude. Immuno-PET (positron emission tomography) could enhance the se nsitivity of this imaging method. Radio-immunoguided surgery and immunophot odetection are attractive techniques still under evaluation. Concerning the rapy, 131-iodine labeled anti-CD20 antibodies gave spectacular results in n on-Hodgkin's B lymphomas. In solid tumors which are less radiosensitive, ra dioimmunotherapy could concern small tumors and need the use of two-steps t argeting and/or alpha emitters radioisotopes. Some other strategies will be described such as bispecific antibodies directed against tumors and immune effector cells, some antibody fragments expressed on T cells called T-bodi es or some biological studies using intrabodies. Published data and works i n progress demonstrate that immunotargeting of tumors will have a growing p lace in the treatment of cancer patients.