Antibody-Drug Conjugates (ADCs) for Personalized Treatment of Solid Tumors: A Review.

Attaching a cytotoxic "payload" to an antibody to form an antibody-drug conjugate (ADC) provides a mechanism for selective delivery of the cytotoxic agent to cancer cells via the specific binding of the antibody to cancer-selective cell surface molecules. The first ADC to receive marketing authorization was gemtuzumab ozogamicin, which comprises an anti-CD33 antibody conjugated to a highly potent DNA-targeting antibiotic, calicheamicin, approved in 2000 for treating acute myeloid leukemia. It was withdrawn from the US market in 2010 following an unsuccessful confirmatory trial.

Pharmacokinetic, biochemical and clinical effects of dimethyltriazenoimidazole-4-carboxamide-bischloroethylnitrosourea combination therapy in patients with advanced breast cancer.

We assessed whether split dosing with the methylating agent DTIC is an effective strategy for inactivating the DNA repair protein O6-alkylguanine DNA-ATase in order to decrease tumour resistance to BCNU. ATase levels in PBMCs were used as a surrogate for tumour ATase depletion to determine whether this correlated with either the pharmacokinetics of DTIC and its major metabolite AIC or other clinical sequelae. Two 1 hr infusions of DTIC (400 mg/m(2)) 4 hr apart followed another 4 hr later by BCNU (75 mg/m(2)) were administered every 6 weeks in 7 patients with heavily pretreated advanced breast cancer.