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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 235-242 |
| Number of pages | 8 |
| Journal | Veterinary Immunology and Immunopathology |
| Volume | 137 |
| Issue number | 3-4 |
| DOIs | |
| State | Published - Oct 2010 |
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Keywords
- Canine
- HLA
- Lym-1
- Lymphoma
- Non-Hodgkin's
ASJC Scopus subject areas
- Immunology
- veterinary(all)
Cite this
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. / Balhorn, Rod L.; Skorupski, Katherine A; Hok, Saphon; Balhorn, Monique Cosman; Guerrero, Teri; Rebhun, Robert B.
In: Veterinary Immunology and Immunopathology, Vol. 137, No. 3-4, 10.2010, p. 235-242.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - 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
AU - Balhorn, Rod L.
AU - Skorupski, Katherine A
AU - Hok, Saphon
AU - Balhorn, Monique Cosman
AU - Guerrero, Teri
AU - Rebhun, Robert B
PY - 2010/10
Y1 - 2010/10
N2 - 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.
AB - 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.
KW - Canine
KW - HLA
KW - Lym-1
KW - Lymphoma
KW - Non-Hodgkin's
UR - http://www.scopus.com/inward/record.url?scp=77956263753&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77956263753&partnerID=8YFLogxK
U2 - 10.1016/j.vetimm.2010.05.014
DO - 10.1016/j.vetimm.2010.05.014
M3 - Article
C2 - 20576295
AN - SCOPUS:77956263753
VL - 137
SP - 235
EP - 242
JO - Veterinary Immunology and Immunopathology
JF - Veterinary Immunology and Immunopathology
SN - 0165-2427
IS - 3-4
ER -