Identification of tumor-binding scFv derived from clonally related B cells in tumor and lymph node of a patient with breast cancer.

Abstract

The purpose of this study was to determine the clonal relationship between B cells within a breast cancer and the B cells in the tumor-draining lymph node (TDLN). We also determined the binding capacity of antibodies derived from these sources to autologous cancer and autologous noncancer breast tissue. Antibody clonality of B cells derived from tumor and lymph node was determined by analyzing heavy and light chain immunoglobulin sequences. The number of shared clonal groups observed between tumor and lymph node antibodies was significant for both heavy (p = 0.004) and light chain (p = 0.012) populations. Panning with phage-displayed single-chain variable fragment libraries derived from the tumor and lymph node B cells resulted in multiple antibodies that bound autologous tumor. Sequence analysis of enriched antibodies recovered after the third round of panning the tumor and TDLN libraries against autologous tumor lysates had a genetic relationship. These results indicate that B cells infiltrating a patient's breast cancer and B cells present in the tumor-draining lymph node are clonally and functionally related.

• Authors: Leah J Novinger, Takamaru Ashikaga, David N Krag
• Journal: Cancer immunology, immunotherapy : CII (Cancer Immunol Immunother) Vol. 64 Issue 1 Pg. 29-39 (Jan 2015) ISSN: 1432-0851 [Electronic] Germany
• PMID: 25261355 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Immunoglobulin Variable Region
• Peptide Library
• Single-Chain Antibodies

Topics

• B-Lymphocytes (immunology, metabolism, pathology)
• Breast Neoplasms (immunology, metabolism, pathology)
• Cells, Cultured
• Clone Cells
• Enzyme-Linked Immunosorbent Assay
• Female
• Humans
• Immunoenzyme Techniques
• Immunoglobulin Variable Region (genetics, immunology, metabolism)
• Lymph Nodes (immunology, metabolism, pathology)
• Lymphocytes, Tumor-Infiltrating (immunology, pathology)
• Peptide Library
• Single-Chain Antibodies (immunology)