IMMUNOTECHNOLOGICAL TRENDS IN RADIOIMMUNOTARGETING - FROM MAGIC BULLET TO SMART BOMB

The impact of recent advances in the chemical and genetic engineering manipulations of antibodies on radioimmunotargeting is reviewed both i n relation to radioimmunoscintigraphy and radioimmunotherapy. The resu lting trends are: (1) the linking of parts of the mouse/rat and human antibody molecule; (2) the creation of molecules with dual antigen or multiple antigen recognition capabilities; (3) the making of smaller a nd smaller antigen recognition molecules; and (4) the development of m olecules with dual capabilities, e.g. antigen recognition and enzyme a ctivity. The various methods of creating antibodies in vitro are revie wed with reference to bacteria, using phage selection and a combinator ial library, mammalian cells, yeast cells and, finally, mice containin g giant yeast artificial chromosomes. The advantages and disadvantages of smaller fragments as well as of the human anti-mouse antibody (HAM A) reaction are discussed and the need for early clinical evaluation a nd widespread availability of the newer antibodies is emphasized. It i s envisaged that these immunotechnological advances will permit the la rge-scale production of precisely engineered humanized antibodies, and the specificity and affinity rate constant of these antibodies can be optimized using in vitro phage selection as well as by computer model ling where the stereo chemistry of the antigen is known precisely.