Immunoconjugates

Figure 69 The boron-rich immunoconjugates (117 and 118) obtained by the tethering of oligomeric nido-carboranyl phosphodiesters to an engineered immunoprotein (a chimeric IgG3 protein). (Adapted from ref. 145.)...

In a somewhat similar scheme, Noguchi et al. (1992) prepared a carboxylate spacer arm by reacting 6-bromohexanoic acid with a dextran polymer. The carboxylate then was aminated with ethylene diamine to form an amine-terminal spacer (Figure 25.15). This dextran derivative finally was reacted with N-Succinimidyl 3-(2-pyridyldithio)propionate (SPDP) (Chapter 5, Section 1.1) to create the desired sulfhydryl-reactive polymer (Section 2.4, this chapter). The SPDP-activated polymer then could be used to prepare an immunoconjugate composed of an antibody against human colon cancer conjugated with the drug mitomycin-C. 

Ashcroft, J.M., Tsyboulski, D.A., Hartman, K.B., Zakharian, T.Y., Marks, J.W., Weisman, R.B., Rosenblumb, M.G., and Wilson, L.J. (2006) Fullerene (C60) immunoconjugates Interaction of water-soluble C60 derivatives with the murine anti-gp240 melanoma antibody. Chem. Comm. 3004-3006. 

Barth, R.F., Adams, D.M., Soloway, A.H., Alam, F., and Darby, M.V. (1994) Boronated starburst den-drimer-monoclonal antibody immunoconjugates Evaluation as a potential delivery system for neutron capture therapy. Bioconjugate Chem. 5, 58-66. 

Boyer, C.M., Lidor, Y., Lottich, S.C., and Bast Jr., R.C. (1988) Antigenic cell surface markers in human solid tumors. Antibody, Immunoconjugates, Radiopharm. 1, 105. 

Foglesong, P.D., Winkler, M.A., Price, J.O., Marshall, G.D., Reagh, S.H., Bush, D.A., Hixson, K.S., and West, W.H. (1989) Preparation and analysis of bifunctional immunoconjugates containing monoclonal antibodies OKT3 and BABR1. Cancer Immunol. Immunother. 30(3), 177-184. 

Li, M., and Meares, C.F. (1993) Synthesis, metal chelate stability studies, and enzyme digestion of a peptide-liked DOTA derivatives and its corresponding radiolabeled immunoconjugates. Bioconjugate Chem. 4, 275-283. 

Noguchi, A., Takahashi, T., Yamaguchi, T., Kitamura, K., Takakura, Y., Hashida, M., and Sezaki, H. (1992) Preparation and properties of the immunoconjugate composed of anti-human colon cancer monoclonal antibody and mitomycin C—Dextran conjugate. Bioconjugate Chem. 3, 132-137. 

Order, S.E. (1989) Therapeutic use of radioimmunoconjugates. Antibody, Immunoconjugates, Radiopharm. 2, 235. 

Rege, K., Patel, S.J., Megeed, Z., and Yarmush, M.L. (2007) Amphipathic peptide-based fusion peptides and immunoconjugates for the targeted ablation of prostate cancer cells. Cancer Res. 67, 6368-6375. 

Reisfeld, R.A., Yang, H.M., Mullet B., Wargalla, U.C., Schrappe, M., and Wrasidlo, W. (1989) Promises, problems, and prospects of monoclonal antibody-drug conjugates for cancer therapy. Antibody, Immunoconjugates, Radiopharm. 2, 217-224. 

Sela, M., and Hurwitz, E. (1987) Conjugates of antibodies with cytotoxic drugs. In Immunoconjugates Antibody Conjugates in Radioimaging and Therapy of Cancer (C.-W. Vogel, ed.), p. 189. Oxford University Press, New York. 

Trail, P.A., Willner, D., Lasch, S.J., Henderson, A.J., Hofstead, S., Casazza, A.M., Firestone, R.A., Hellstrom, I., and Hellstrom, K.E. (1993) Cure of xenografted human carcinomas by BR96-doxoru-bicin immunoconjugates. Science 261, 212-215. 

Zara, J.J. et al. (1991) A carbohydrate-directed heterobifunctional cross-linking reagent for the synthesis of immunoconjugates. Anal. Biochem. 194, 156-162. 

Ashcroft JM, Tsyboulski DA, Hartman KB, Zakharian TY, Marks JW, Weisman RB, Rosenblum MG, Wilson LJ (2006). Fullerene (CM ) immunoconjugates interaction of water-soluble Cm derivatives with the murine anti-gp240 melanoma antibody. Chem. Comm. 28 3004-3006. 

MAb-based constructs represent, as described, a heterogeneous class of anti-tumour agents with remarkable efficacy in the treatment of experimental cancers in animals. Several MAb and immunoconjugates have been evaluated further in cancer patients, and the results have indicated that some have activity at safe doses. 

The immunoconjugate of doxorubicin with a chimeric anti-Le -related, tumour-associated antigen expressed on most human carcinomas, was evaluated in phase I [132] and phase II [133] clinical trials. The phase II trial performed in patients with metastatic breast carcinoma showed low clinical response rates. These data together with tumour biopsy analysis suggest that the dose that could be safely administered was insufficient to maintain the intra-tu-... 

Damle NK, Frost P. Antibody-targeted chemotherapy with immunoconjugates of calicheamicin. Curr Opin Pharmacol 20(B 3 386-90. 

Rakestraw et al. [197] recently demonstrated the efficacy of chlorin e6 immunoconjugates through a clonogenic assay. Other examples of the use of clonogenic assays may be found [198, 199]. 

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