Precision medicine in clinical oncology: the journey from IgG antibody to IgE

Curr Opin Allergy Clin Immunol. 2020 Jun;20(3):282-289. doi: 10.1097/ACI.0000000000000637.

Abstract

Purpose of review: Cancer is one of the leading causes of death and the incidence rates are constantly rising. The heterogeneity of tumors poses a big challenge for the treatment of the disease and natural antibodies additionally affect disease progression. The introduction of engineered mAbs for anticancer immunotherapies has substantially improved progression-free and overall survival of cancer patients, but little efforts have been made to exploit other antibody isotypes than IgG.

Recent findings: In order to improve these therapies, 'next-generation antibodies' were engineered to enhance a specific feature of classical antibodies and form a group of highly effective and precise therapy compounds. Advanced antibody approaches include among others antibody-drug conjugates, glyco-engineered and Fc-engineered antibodies, antibody fragments, radioimmunotherapy compounds, bispecific antibodies and alternative (non-IgG) immunoglobulin classes, especially IgE.

Summary: The current review describes solutions for the needs of next-generation antibody therapies through different approaches. Careful selection of the best-suited engineering methodology is a key factor in developing personalized, more specific and more efficient mAbs against cancer to improve the outcomes of cancer patients. We highlight here the large evidence of IgE exploiting a highly cytotoxic effector arm as potential next-generation anticancer immunotherapy.

MeSH terms

  • Antibodies, Bispecific / therapeutic use
  • Antibodies, Monoclonal / therapeutic use
  • Antineoplastic Agents, Immunological / therapeutic use*
  • Drug Resistance, Neoplasm / genetics
  • Humans
  • Immunoconjugates / therapeutic use
  • Immunoglobulin E / therapeutic use
  • Immunoglobulin Fc Fragments / therapeutic use
  • Medical Oncology / methods*
  • Medical Oncology / trends
  • Neoplasms / drug therapy*
  • Neoplasms / genetics
  • Neoplasms / immunology
  • Neoplasms / mortality
  • Precision Medicine / methods*
  • Precision Medicine / trends
  • Progression-Free Survival
  • Protein Engineering
  • Radioimmunotherapy / methods*
  • Radioimmunotherapy / trends
  • Tumor Escape / genetics

Substances

  • Antibodies, Bispecific
  • Antibodies, Monoclonal
  • Antineoplastic Agents, Immunological
  • Immunoconjugates
  • Immunoglobulin Fc Fragments
  • Immunoglobulin E