title: Using the Lessons Learned From the Clinic to Improve the Preclinical Development of Antibody Drug Conjugates.
abstract: The treatment options for cancer patients include surgery, chemotherapeutics, radiation therapy, antibody therapy and various combinations of these therapies. The challenge with each therapy is finding the balance between maximizing the anti-tumor efficacy while minimizing the dose limiting toxicities. Antibodies, unlike small molecule chemotherapeutics, selectively bind to cell surface tumor antigens and can be used to deliver radionucleotides or small molecule chemotherapeutic drugs directly to the tumor. Advances in antibody engineering, linker chemistry and the identification of potent cytotoxic drugs led to the recent approval of two antibody drug conjugates to treat breast cancer and lymphoma patients. We will discuss how the observations from the clinical development of antibody drug conjugates can guide the preclinical development of the next generation of antibody drug conjugates.
authors.affiliation: Agensys, Inc, 1800 Stewart Street, Santa Monica, California, 90404, USA. djackson@agensys.com.
authors.forename: Dowdy
authors.initials: D
authors.lastname: Jackson
authors.affiliation: Agensys, Inc, 1800 Stewart Street, Santa Monica, California, 90404, USA.
authors.forename: David
authors.initials: D
authors.lastname: Stover
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002986:Clinical Trials as Topic; D055808:Drug Discovery / Q000379:methods*; D004353:Drug Evaluation, Preclinical; D006801:Humans; D018796:Immunoconjugates / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D018796:Immunoconjugates
keywords: antibody drug conjugate; preclinical; site specific