Nanobody-based heavy chain antibodies and chimeric antibodies

Immunol Rev. 2024 Nov;328(1):466-472. doi: 10.1111/imr.13385. Epub 2024 Aug 30.

Abstract

Nanobodies are the products of an intriguing invention in the evolution of immunoglobulins. This invention can be traced back approximately 45 million years to the common ancestor of extant dromedaries, camels, llamas, and alpacas. Next to conventional heterotetrameric H2L2 antibodies, these camelids produce homodimeric nanobody-based heavy chain antibodies, composed of shortened heavy chains that a lack the CH1 domain. Nanobodies against human target antigens are derived from immunized animals and/or synthetic nanobody libraries. As a robust, highly soluble, single immunoglobulin domain, a nanobody can easily be fused to another protein, for example to another nanobody and/or the hinge and constant domains of other immunoglobulins. Nanobody-derived heavy chain antibodies hold promise as a new form of immunotherapeutics.

Keywords: heavy‐chain antibody; immunoglobulin; immunotherapeutic; nanobody.

Publication types

  • Review

MeSH terms

  • Animals
  • Camelidae / immunology
  • Humans
  • Immunoglobulin Heavy Chains* / genetics
  • Immunoglobulin Heavy Chains* / immunology
  • Immunoglobulin Heavy Chains* / therapeutic use
  • Immunotherapy / methods
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / immunology
  • Recombinant Fusion Proteins / therapeutic use
  • Single-Domain Antibodies* / genetics
  • Single-Domain Antibodies* / immunology
  • Single-Domain Antibodies* / therapeutic use

Substances

  • Immunoglobulin Heavy Chains
  • Recombinant Fusion Proteins
  • Single-Domain Antibodies