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.
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.
Balhorn
Rod L
RL
Department of Applied Science, University of California, Davis, Davis, CA 95616, USA.
Skorupski
Katherine A
KA
Hok
Saphon
S
Balhorn
Monique Cosman
MC
Guerrero
Teri
T
Rebhun
Robert B
RB
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D058846:Antibodies, Monoclonal, Murine-Derived; D004283:Dog Diseases / Q000628:therapy*; D004285:Dogs; D000939:Epitopes; D006684:HLA-DR Antigens / Q000737:chemistry / Q000235:genetics; D059810:HLA-DR Serological Subtypes; D059811:HLA-DRB1 Chains; D006801:Humans; D016393:Lymphoma, B-Cell / Q000276:immunology / Q000628:therapy / Q000662:veterinary*; D008228:Lymphoma, Non-Hodgkin / Q000276:immunology / Q000628:therapy*; D008969:Molecular Sequence Data
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D000939:Epitopes; D006684:HLA-DR Antigens; D059810:HLA-DR Serological Subtypes; C421823:HLA-DR10 antigen; D059811:HLA-DRB1 Chains; C410509:Lym-1 monoclonal antibody