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- W4255965233 abstract "We have developed a new modular affinity system for the 2-step delivery of functional molecules to target cells. The system is based on the tautomer-specific monoclonal antibody (MAb) EM-6–47, which binds to 3- and 3,8-substituted adenines with high affinity (Ka > 109 l/mol) without cross-reacting with naturally occurring purine derivatives. This MAb serves as the hapten-specific fusion partner to produce bispecific MAbs (bs-MAbs) recognizing a target cell antigen and a low-m.w. hapten as carrier molecule for, e.g., radionuclides. Either the C-8 or the N-3 position of adenines can be used for conjugation with effector molecules; the remaining position may be substituted with different moieties to modulate the pharmacokinetics of the haptens. Different 3- and 3,8-substituted adenines conjugated to the chelates DOTA and DTPA or to the drug daunomycin were synthesized. Adenine-chelate derivatives were efficiently labeled with 111In and 90Y, while high-affinity binding of 3-substituted adenines to MAb EM-6–47 remained almost unaffected by the conjugation to radiochelates. To confirm the validity of the delivery system, a prototype bs-MAb, EM-168–47, was generated by somatic cell fusion of MAb EM-6–47 and MAb EM-168–2, the latter recognizing a surface antigen on canine hematopoietic cells. Two-step targeting assays in vitro verified the bs-MAb-mediated, dose-dependent delivery of 111In-labeled adenine-chelate derivatives to myeloid cells. This system represents a powerful tool for new pre-targeting approaches relying on bs-MAbs and low-m.w. haptens. Suitable cellular antigens can be targeted by fusing the appropriate MAbs with hapten-specific MAb EM-6–47, and tailor-made 3-substituted adenines may be labeled with diagnostic or therapeutic radionuclides, cytotoxic drugs or other functional molecules. Int. J. Cancer 77:610–619, 1998. © 1998 Wiley-Liss, Inc." @default.
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- W4255965233 date "1998-08-12" @default.
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- W4255965233 title "New modular delivery system for diagnostic and therapeutic pre‐targeting using tautomer‐specific monoclonal antibody EM‐6‐47 and 3‐substituted adenines" @default.
- W4255965233 doi "https://doi.org/10.1002/(sici)1097-0215(19980812)77:4<610::aid-ijc22>3.3.co;2-b" @default.
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