Antibody constructs for radioimmunodiagnosis and treatment of human pancreatic cancer.

Abstract

Pancreatic cancer (PC) is a common disease that is seldom cured. Current approaches to the treatment of PC are not effective because the non-specific nature of both chemotherapy and external beam radiation results in toxicity to normal tissue. Monoclonal antibodies (MAbs) can be used as selective carriers for delivering radionuclides, toxins, or cytotoxic drugs to malignant cell populations. Therefore, MAb-technology has led to a significant amount of research in targeted therapy. Targeted therapy would generally allow the concentration of cytotoxic agents in tumors and would markedly lessen the toxicity to normal tissues, which limits the dosage and effectiveness of systemically administered drugs. A variety of MAbs are being pre-clinically evaluated for the diagnosis and treatment of PC. Novel recombinant antibody constructs hold a promising future in both the diagnosis and treatment of cancer. By genetic-engineering methods, several high affinity antibody fragments with optimum tumor targeting properties, such as higher functional affinity (divalent and multivalent scFvs) and blood residence time (good tumor localization with high radiolocalization index), have been generated. Animal models have permitted the in vivo assessment of these antibody-based reagents, therapeutic/diagnostic radionuclide, radiolabeling conditions, and efficacy of administration regimes. For PC, immunoscintigraphy using MAbs has taken new strides. The use of MAbs and their fragments for radioimmunoguided surgery and therapy of PC has shown encouraging results at preclinical levels and warrants further attention.