A novel platform for mining the repertoire of antigen-specific B cells

DESCRIPTION (provided by applicant): Cancer remains a significant threat to the health and economy of today's society. Advances in cancer research are key to cancer biomarker discovery, development of rapid and reliable methods of cancer-specific diagnosis, and development of new treatments. Multi-analyte detection platforms such as protein microarrays have potential for fast, high-throughput analysis of complex samples for small molecules and proteins of interest. The next few years will likely yield rapid advancement in the use of these platforms for cancer biomarker discovery and early-stage diagnosis of different cancers. Despite the advancement of multi-analyte platforms, however, the overall performance and usefulness of these approaches depends heavily on the quality of the monoclonal antibodies used to capture and detect molecules of interest on the microarray surface. Successful microarray development requires screening numerous monoclonal antibodies for affinity, specificity, cross-reactivity, and platform compatibility. For a given diagnostic cancer target, dozens of monoclonal antibodies may need to be screened and, thus the techniques used to generate the monoclonal antibodies must be able to generate a panel of highly diverse target-specific monoclonal antibodies. Because of limitations in current monoclonal antibody development methods, such panels of target-specific monoclonal antibodies often are not available and are prohibitively expensive to make. The overall objective of this Phase I application is to generate a unique technology for mining the clonal repertoire of B cells from immunized mice and generating panels of antigen-specific monoclonal antibodies against targets of interest. NeoClone proposes to adapt its successful ABL-MYC retroviral technology to develop a novel in vitro platform for the clonal expansion, selection, and transformation of antigen-specific B cells. This platform will enable unprecedented clonal diversity, generating panels of monoclonal antibodies that can be tested for specific epitope identification, affinity, and platform compatibility. In addition, the in vitro methods proposed here will allow for the selection of rare clones, thereby enabling NeoClone to develop antibodies against important targets where traditional methods have failed. The rapid growth of new platforms for detecting rare targets in complex samples demands the parallel development of new technologies for generating affinity reagents against those targets. Any new technology must produce reagents with high affinities, high selectivity, and high clonal diversity. NeoClone's unique in vitro ABL-MYC technology can meet these requirements. Monoclonal antibodies are essential for helping to discover cancer in the body, especially in early stages (biomarkers), develop ways to diagnose cancer, and to find new treatments for the disease. NeoClone proposes to develop a new way to create large numbers of high-quality, diverse, cancer-specific monoclonal antibodies both quickly and cost-effectively. This technology can potentially advance new methods for diagnosing cancer, such as antibody microarrays, which need high-quality cancer biomarker-specific antibodies to move into the clinic.