Affinity of the alpha4-beta1 integrin-targeting peptide LLP2A to canine lymphoma

Allison Zwingenberger, Michael S Kent, Changying Shi, Sandra L. Taylor, Xiucui Chen, Kit Lam

Research output: Contribution to journalArticle

11 Scopus citations

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 languageEnglish (US)
Pages (from-to)298-304
Number of pages7
JournalVeterinary Immunology and Immunopathology
Volume145
Issue number1-2
DOIs
StatePublished - Jan 15 2012

Keywords

  • Canine
  • LLP2A
  • Lymphoma
  • Non-Hodgkin's
  • Peptidomimetic

ASJC Scopus subject areas

  • Immunology
  • veterinary(all)

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