Antineoplastic immunoconjugates and immunotoxins

Research output: Contribution to journalArticle

Abstract

This paper discusses the scientific rationale, synthesis, therapeutic utility and clinical limitations of cancer chemotherapy with antineoplastic drugs or toxins covalently linked to monoclonal antibodies directed against tumor cell antigens. Chemical issues that must be considered when designing an effective antineoplastic immunoconjugate or immunotoxin (including purity, functional group suitability for conjugation, antigenic specificity, stability, solubility, potency and immunogenicity) are discussed. Synthetic strategies used in the gener ation of immunoconjugates and immunotoxins are presented, and the use of flexible spacer molecules as adjuncts to conjugation is described. The use of targeting antibodies conjugated to enzymes that selectively activate antineoplastic prodrugs on or near cancer cells (known as antibody-directed enzyme pro-drug therapy, or ADEPT) is also addressed. The paper ends with a brief discussion on the development of chimeric and humanized antibodies, which are designed to decrease the incidence of the human anti-mouse antibody (HAMA) response that is so often responsible for treatment failure with these targeted anticancer agents.

Original languageEnglish (US)
Pages (from-to)197-204
Number of pages8
JournalAmerican journal of pharmaceutical education
Volume64
Issue number2
StatePublished - Jan 1 2000

All Science Journal Classification (ASJC) codes

  • Education
  • Pharmacology, Toxicology and Pharmaceutics(all)

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