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 in relation to radioimmunoscintigraphy and radioimmunotherapy. The resulting 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 and smaller antigen recognition molecules; and (4) the development of molecules with dual capabilities, e.g. antigen recognition and enzyme activity. The various methods of creating antibodies in vitro are reviewed with reference to bacteria, using phage selection and a combinatorial library, mammalian cells, yeast cells and, finally, mice containing giant yeast artificial chromosomes. The advantages and disadvantages of smaller fragments as well as of the human anti-mouse antibody (HAMA) reaction are discussed and the need for early clinical evaluation and widespread availability of the newer antibodies is emphasized. It is envisaged that these immunotechnological advances will permit the large-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 modelling where the stereo chemistry of the antigen is known precisely.
Hazra
D K
DK
Postgraduate Department of Medicine, S.N. Medical College, Agra, India.
Britton
K E
KE
Lahiri
V L
VL
Gupta
A K
AK
Khanna
P
P
Saran
S
S
D000818:Animals; D000906:Antibodies / Q000737:chemistry / Q000235:genetics; D000888:Antibodies, Anti-Idiotypic / Q000096:biosynthesis; D018033:Antibodies, Bispecific / Q000627:therapeutic use; D000916:Antibody Diversity; D006801:Humans; D007158:Immunologic Techniques / Q000639:trends; D051379:Mice; D015202:Protein Engineering; D016719:Radioimmunodetection / Q000009:adverse effects / Q000639:trends*; D016499:Radioimmunotherapy / Q000009:adverse effects / Q000639:trends*; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology; D013045:Species Specificity
D000906:Antibodies; D000888:Antibodies, Anti-Idiotypic; D018033:Antibodies, Bispecific; D011993:Recombinant Fusion Proteins