THE EFFECTS OF CLINICALLY RELEVANT HYPERTHERMIC TEMPERATURES ON THE KINETIC BINDING PARAMETERS OF A MONOCLONAL-ANTIBODY

Hyperthermia is a therapeutic modality under investigation for its abi lity to increase absolute levels of tumor uptake of radiolabeled monoc lonal antibodies (MAbs). We have investigated whether hyperthermia may affect the binding parameters of MAbs. The effects of clinically rele vant levels of hyperthermia on the kinetic binding parameters were inv estigated for 81C6, an antibody undergoing Phase I/II clinical trials for the treatment of brain tumors and neoplastic meningitis. No obviou s effects of temperature in either the association or dissociation rat e constants, nor in the equilibrium constants, were apparent between 3 7 degrees and 45 degrees C. The improved binding stability of the biva lent form of the MAb was apparent when compared with its monovalent Fa b fragment.