A selective high affinity ligand (SHAL) designed to bind to an over-expressed human antigen on non-Hodgkin's lymphoma also binds to canine B-cell lymphomas

Vet Immunol Immunopathol. 2010 Oct 15;137(3-4):235-42. doi: 10.1016/j.vetimm.2010.05.014. Epub 2010 Jun 2.

Abstract

Therapies using antibodies directed against cell surface proteins have improved survival for human patients with non-Hodgkin's lymphoma (NHL). It is possible that similar immuno-therapeutic approaches may also benefit canine NHL patients. Unfortunately, variability between human and canine epitopes often limits the usefulness of such therapies in pet dogs. The Lym-1 antibody recognizes a unique epitope on HLA-DR10 that is expressed on the majority of human B-cell malignancies. The Lym-1 antibody has now been observed to bind to dog lymphocytes and B-cell NHL. Sequence comparisons and computer modeling of a human and three canine DRB1 proteins identified several orthologs of human HLA-DR10 expressed by dog lymphocytes. Immuno-staining confirmed the presence of proteins containing the Lym-1 epitope on dog lymphocytes and B-cell NHL. In addition, a selective high affinity ligand (SHAL) SH-7139 designed to bind within the Lym-1 epitope of HLA-DR10 was also observed to bind to canine B-cell NHL tissue. This SHAL, which is selectively cytotoxic to cells expressing HLA-DR10 and has been shown to cure mice bearing human B-cell lymphoma xenografts, may prove useful in treating B-cell malignancies in pet dogs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antibodies, Monoclonal / immunology*
  • Antibodies, Monoclonal, Murine-Derived
  • Dog Diseases / therapy*
  • Dogs
  • Epitopes
  • HLA-DR Antigens / chemistry
  • HLA-DR Antigens / genetics
  • HLA-DR Serological Subtypes
  • HLA-DRB1 Chains
  • Humans
  • Lymphoma, B-Cell / immunology
  • Lymphoma, B-Cell / therapy
  • Lymphoma, B-Cell / veterinary*
  • Lymphoma, Non-Hodgkin / immunology
  • Lymphoma, Non-Hodgkin / therapy*
  • Molecular Sequence Data

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Murine-Derived
  • Epitopes
  • HLA-DR Antigens
  • HLA-DR Serological Subtypes
  • HLA-DR10 antigen
  • HLA-DRB1 Chains
  • Lym-1 monoclonal antibody