title: Affinity of the alpha4-beta1 integrin-targeting peptide LLP2A to canine lymphoma.
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.
authors.affiliation: Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California, Davis, CA 95616, USA. azwingen@ucdavis.edu
authors.forename: Allison L
authors.initials: AL
authors.lastname: Zwingenberger
authors.forename: Michael S
authors.initials: MS
authors.lastname: Kent
authors.forename: Changying
authors.initials: C
authors.lastname: Shi
authors.forename: Sandra L
authors.initials: SL
authors.lastname: Taylor
authors.forename: Xiucui
authors.initials: X
authors.lastname: Chen
authors.forename: Kit S
authors.initials: KS
authors.lastname: Lam
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D004151:Dipeptides / Q000276:immunology / Q000378:metabolism*; D004283:Dog Diseases / Q000276:immunology* / Q000378:metabolism; D004285:Dogs; D005260:Female; D005434:Flow Cytometry / Q000662:veterinary; D039041:Integrin alpha4beta1 / Q000276:immunology / Q000378:metabolism*; D016131:Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D008223:Lymphoma / Q000276:immunology / Q000378:metabolism / Q000662:veterinary*; D016399:Lymphoma, T-Cell / Q000276:immunology / Q000378:metabolism / Q000662:veterinary; D008297:Male; D010671:Phenylurea Compounds / Q000276:immunology / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism
chemical_list: D004151:Dipeptides; D039041:Integrin alpha4beta1; C512274:LLP2A compound; D010671:Phenylurea Compounds