The palmotylated glycoprotein A33 (gpA33) is a cell-surface differentiation antigen that belongs to the immunoglobulin superfamily (1, 2). This antigen is expressed primarily in the normal intestine and in >95% of colon tumors, and it has not been detected in any other tissue (1, 2). Because of its presence only in the intestine or in tumors in the intestine, the gpA33 has been evaluated as a target for the detection and radioimmunotherapy of colon cancer tumors (2). The biodistribution of a radioiodinated humanized monoclonal antibody (Ab) directed against the human gpA33 antigen (huA33) is discussed in a separate MICAD chapter (3). It was reported that the labeled Ab used to treat the colon cancers bound to the entire intestinal tissue, including the tumors; however, although the radioactivity persisted in the tumors for at least 6 weeks, the label was lost from the normal gut tissue within 1 week after administration (1-3). The more rapid clearance of a radioiodinated huA33 from the normal intestinal tissue was observed to correspond to the turnover period of basal colonocytes in this tissue (4).
Despite the extensive use of immunotherapy to treat cancers, the efficacy of this regimen is limited by the fact that not all individuals are responsive to this therapy. This is either due to the lack of or irresponsiveness of the receptors (or antigens) to which the Abs are directed. Also, because of its large size, the Ab may not be able to penetrate solid cancerous tumors completely, remain in blood circulation for extended periods, or may not be effective due to other factors as described by von Mehren et al. (5). As an alternative to Abs, investigators have developed Ab fragments such as the single chain variable fragments (scFv), which are much smaller (~30 kDa) than intact Abs (~150 kDa), contain the antigen-binding site, exhibit high tumor penetration, generate excellent tumor/normal tissue concentration ratios, and show rapid clearance through the kidneys (6, 7). Several scFv fragments targeted toward different antigens are under evaluation in
Biodistribution and efficacy of [131I]A33scFv::CDy, a recombinant antibody-enzyme protein for colon cancer.Int J Oncol. 2008 Apr;32(4):925-30. Int J Oncol. 2008. PMID: 18360720
Design, construction, and in vitro analysis of A33scFv::CDy, a recombinant fusion protein for antibody-directed enzyme prodrug therapy in colon cancer.Int J Oncol. 2007 Oct;31(4):951-7. Int J Oncol. 2007. PMID: 17786329
125I-Labeled murine anti-CD20 antigen monoclonal antibody NuB2 conjugated to one or three octaarginine (maleimide-(6-aminocaproic acid)2-(D-Arg)8-(D-Tyr)) peptide chains.2010 Dec 8 [updated 2010 Dec 28]. In: Molecular Imaging and Contrast Agent Database (MICAD) [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2004–2013. Molecular Imaging and Contrast Agent Database (MICAD). 2004–2013. PMID: 21210565 Free Books & Documents. Review.
Radioiodinated humanized monoclonal antibody A33.2007 Sep 16 [updated 2007 Oct 22]. In: Molecular Imaging and Contrast Agent Database (MICAD) [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2004–2013. Molecular Imaging and Contrast Agent Database (MICAD). 2004–2013. PMID: 20641323 Free Books & Documents. Review.
[111In]-Labeled divalent Fab fragment of chimeric monoclonal antibody cG250 directed against carbonic anhydrase IX.2010 Aug 11 [updated 2010 Sep 2]. In: Molecular Imaging and Contrast Agent Database (MICAD) [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2004–2013. Molecular Imaging and Contrast Agent Database (MICAD). 2004–2013. PMID: 20827820 Free Books & Documents. Review.