00888-A: Generation of Canine Single Chain Fragment Variable Antibody Libraries for the Identification and Targeting of Tumor-Associated Antigens in the Dog

Abstract

Cancer is the leading cause of disease related death in our current canine pet population. The mainstay of cancer therapy is the systemic administration of chemotherapeutic agents that inhibit cell division and induce cell death. These agents however are not tumor-specific and frequently cause adverse side effects which limit the dose that can be given and the therapeutic efficacy of the agent. It is the aim of this proposal to develop a method to generate synthetic antibodies that will in the future be used to identify canine cancer targets and deliver cytotoxic agents directly to canine tumors, resulting in reduced systemic toxicity and increased therapeutic efficacy of the agent against the tumor. White blood cells known as B lymphocytes produce antibodies and are part of the body�s immune defense system which is involved in the recognition and destruction of invading infectious agents and tumors. B cells recognize different targets via different B cell receptors (antibodies) displayed on their surface and the specificity of each B cell receptor/antibody is determined by the genetic code located within the B cell itself. Molecular techniques performed on a peripheral blood sample can be used to clone these receptors and generate synthetic antibodies that can be screened to determine what their target molecules are. Recent data using this technology have shown that human cancer patients generate antibody responses against their own tumors and this has led to the identification of tumor-associated molecules that can be targeted by the synthetic antibodies. In this proposal we aim to take advantage of the recently sequenced canine genome in order to develop molecular techniques that will allow us to examine the immunological responses that canine caner patients make to their own tumors. In the future, these techniques will be used to identify tumor molecules present in canine cancer patients and to generate synthetic canine antibodies that could be used therapeutically in vivo to target them.

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