Abstract
Lymphoma is an important disease in dogs and people, with similar biological characteristics. We tested the binding affinity of a peptidomimetic LLP2A, previously shown to bind the alpha4-beta1 integrin on human lymphoma cell lines, to lymphocytes of dogs with spontaneously occurring lymphoma. Fine needle aspirates of lymph nodes from 32 dogs with B-cell lymphoma and 7 dogs with T-cell lymphoma were evaluated using flow cytometry. For B cells, the lowest MFI levels were in unlabeled, non-neoplastic lymphocytes. The highest median fluorescent intensity (MFI) levels occurred in LLP2A-labeled lymphoma cells from dogs that had not received chemotherapy followed by labeled lymphoma cells from dogs that had received chemotherapy. The fluorescence profile of the T-cell samples was similar although many of the differences were not statistically significant, likely due to low sample number. Specifically, LLP2A-labeled T-cell lymphoma cells had a significantly higher MFI compared to unlabeled non-neoplastic lymphocytes. LLP2A affinity was not significantly different in unlabeled and labeled T-cell lymphoma cells, and labeled non-neoplastic lymphocytes. For both B and T cells, labeling with LLP2A tended to increase MFI in both normal and lymphoma cells. Lymphoma cells had higher mean MFI levels than non-neoplastic lymphocytes, and chemotherapy acted to decrease MFI. In summary, these data demonstrate that LLP2A has affinity to canine lymphoma cells and indicates expression of the alpha4-beta1 integrin on these cells. In fact, LLP2A preferentially binds neoplastic B-cells, suggesting that this small molecule may be of use in cross-species clinical trials of targeted therapeutics.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 298-304 |
| Number of pages | 7 |
| Journal | Veterinary Immunology and Immunopathology |
| Volume | 145 |
| Issue number | 1-2 |
| DOIs | |
| State | Published - Jan 15 2012 |
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Keywords
- Canine
- LLP2A
- Lymphoma
- Non-Hodgkin's
- Peptidomimetic
ASJC Scopus subject areas
- Immunology
- veterinary(all)
Cite this
Affinity of the alpha4-beta1 integrin-targeting peptide LLP2A to canine lymphoma. / Zwingenberger, Allison; Kent, Michael S; Shi, Changying; Taylor, Sandra L.; Chen, Xiucui; Lam, Kit.
In: Veterinary Immunology and Immunopathology, Vol. 145, No. 1-2, 15.01.2012, p. 298-304.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Affinity of the alpha4-beta1 integrin-targeting peptide LLP2A to canine lymphoma
AU - Zwingenberger, Allison
AU - Kent, Michael S
AU - Shi, Changying
AU - Taylor, Sandra L.
AU - Chen, Xiucui
AU - Lam, Kit
PY - 2012/1/15
Y1 - 2012/1/15
N2 - Lymphoma is an important disease in dogs and people, with similar biological characteristics. We tested the binding affinity of a peptidomimetic LLP2A, previously shown to bind the alpha4-beta1 integrin on human lymphoma cell lines, to lymphocytes of dogs with spontaneously occurring lymphoma. Fine needle aspirates of lymph nodes from 32 dogs with B-cell lymphoma and 7 dogs with T-cell lymphoma were evaluated using flow cytometry. For B cells, the lowest MFI levels were in unlabeled, non-neoplastic lymphocytes. The highest median fluorescent intensity (MFI) levels occurred in LLP2A-labeled lymphoma cells from dogs that had not received chemotherapy followed by labeled lymphoma cells from dogs that had received chemotherapy. The fluorescence profile of the T-cell samples was similar although many of the differences were not statistically significant, likely due to low sample number. Specifically, LLP2A-labeled T-cell lymphoma cells had a significantly higher MFI compared to unlabeled non-neoplastic lymphocytes. LLP2A affinity was not significantly different in unlabeled and labeled T-cell lymphoma cells, and labeled non-neoplastic lymphocytes. For both B and T cells, labeling with LLP2A tended to increase MFI in both normal and lymphoma cells. Lymphoma cells had higher mean MFI levels than non-neoplastic lymphocytes, and chemotherapy acted to decrease MFI. In summary, these data demonstrate that LLP2A has affinity to canine lymphoma cells and indicates expression of the alpha4-beta1 integrin on these cells. In fact, LLP2A preferentially binds neoplastic B-cells, suggesting that this small molecule may be of use in cross-species clinical trials of targeted therapeutics.
AB - Lymphoma is an important disease in dogs and people, with similar biological characteristics. We tested the binding affinity of a peptidomimetic LLP2A, previously shown to bind the alpha4-beta1 integrin on human lymphoma cell lines, to lymphocytes of dogs with spontaneously occurring lymphoma. Fine needle aspirates of lymph nodes from 32 dogs with B-cell lymphoma and 7 dogs with T-cell lymphoma were evaluated using flow cytometry. For B cells, the lowest MFI levels were in unlabeled, non-neoplastic lymphocytes. The highest median fluorescent intensity (MFI) levels occurred in LLP2A-labeled lymphoma cells from dogs that had not received chemotherapy followed by labeled lymphoma cells from dogs that had received chemotherapy. The fluorescence profile of the T-cell samples was similar although many of the differences were not statistically significant, likely due to low sample number. Specifically, LLP2A-labeled T-cell lymphoma cells had a significantly higher MFI compared to unlabeled non-neoplastic lymphocytes. LLP2A affinity was not significantly different in unlabeled and labeled T-cell lymphoma cells, and labeled non-neoplastic lymphocytes. For both B and T cells, labeling with LLP2A tended to increase MFI in both normal and lymphoma cells. Lymphoma cells had higher mean MFI levels than non-neoplastic lymphocytes, and chemotherapy acted to decrease MFI. In summary, these data demonstrate that LLP2A has affinity to canine lymphoma cells and indicates expression of the alpha4-beta1 integrin on these cells. In fact, LLP2A preferentially binds neoplastic B-cells, suggesting that this small molecule may be of use in cross-species clinical trials of targeted therapeutics.
KW - Canine
KW - LLP2A
KW - Lymphoma
KW - Non-Hodgkin's
KW - Peptidomimetic
UR - http://www.scopus.com/inward/record.url?scp=84856543584&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84856543584&partnerID=8YFLogxK
U2 - 10.1016/j.vetimm.2011.11.018
DO - 10.1016/j.vetimm.2011.11.018
M3 - Article
VL - 145
SP - 298
EP - 304
JO - Veterinary Immunology and Immunopathology
JF - Veterinary Immunology and Immunopathology
SN - 0165-2427
IS - 1-2
ER -