DEVELOPMENT AND CHARACTERIZATION OF NOVEL MONOCLONAL ANTIBODIES TARGETING CARBOHYDRATE ANTIGENS IN CANCER

Since the first description by Kohler and Milstein in 1975, monoclonal antibodies (mAbs) have quickly become a key component in the select targeting, blocking and clearance of many diseases by the immune system. Today mAbs constitute the fastest growing segment of immunotherapy in the diagnosis and treatment of cancer. These unique and novel proteins are capable of binding to specific antigens in vivo and flagging cells displaying them for destruction. Over the last two decades, numerous studies have shown that a variety of cancers alter their glycosylation patterns resulting in the extracellular presentation of tumor-associated carbohydrate antigens (TACAs). Despite promising research into anti-TACA therapeutics over the years, only one anti-TACA monoclonal antibody is approved for cancer treatment. In an effort to advance immunotherapy, the objective of this research was to identify, develop, and characterize novel monoclonal antibodies targeting saccharide antigens. Here we show PD-1-/- mice on a C57BL/6 background can be used to generate an immunogenic response to desialylated bovine submaxillary mucin (dBSM). From these we produced anti-GlcNAc (N-Acetyl-D-Glucosamine) and anti-GalNAc (N-Acetyl-D-Galactosamine) mAbs capable of binding to TA3-Ha murine adenocarcinoma. These novel mAbs open a gateway to understanding alternative targeting of cancer cells and expand opportunities in immunotherapy and theranostics.

Grantor dc:publisher

Wake Forest University

Year dc:date.issued

2016

Author dc:creator

• Littrell, Chad

• Cancer

Language dc:language.iso

en

Handle dc:identifier.uri

http://hdl.handle.net/10339/59292

OAI identifier oai:identifier

oai:wakespace.lib.wfu.edu:10339/59292