Determination of pharmacokinetic values of calicheamicin-antibody conjugates in mice by plasmon resonance analysis of small (5 microl) blood samples.

Purpose: The present study aims to establish a method that provides fast, precise and reproducible pharmacokinetic (PK) parameters of antibody-calicheamicin conjugates. The method should discriminate between PK of the antibody moiety and PK of the conjugated calicheamicin (CM).

Methods: The conjugates gemtuzumab ozogamicin (CMA-676, Mylotarg) or inotuzumab ozogamicin (CMC-544) were injected in the tail vein of nude mice.

Antibody-targeted chemotherapy with the calicheamicin conjugate hu3S193-N-acetyl gamma calicheamicin dimethyl hydrazide targets Lewisy and eliminates Lewisy-positive human carcinoma cells and xenografts.

Purpose: Linking a cytotoxic anticancer drug to an antibody that recognizes a tumor-associated antigen can improve the therapeutic index of the drug. We asked whether a conjugate of the cytotoxic antibiotic N-acetyl gamma calicheamicin dimethyl hydrazide (CalichDMH) and an antibody recognizing Lewis(y) (Le(y)) antigen could eliminate carcinomas that express Le(y). Because Le(y) is highly expressed on carcinomas of colon, breast, lung, ovary, and prostate, a CalichDMH conjugate targeting Le(y) could provide a treatment option for various cancers.