Abstract P2-16-01: Discovery of fully human monoclonal antibodies as therapeutic candidates for the treatment of HER2-negative breast cancer

Abstract

Abstract Unlike HER2-positive breast cancer, there are limited treatment options for patients diagnosed with triple negative and endocrine resistant HER2-negative breast cancer, and as such HER2-negative breast cancer represents a significant unmet medical need. The goal of this work is to use Theraclone’s proprietary I-STAR platform to mine the memory B cell immune repertoire of breast cancer patients for the discovery of therapeutically relevant monoclonal antibodies (mAbs) and targets that may be exploited as candidates for treatment of HER2-negative breast cancer. Matched serum and PBMC samples were collected from breast cancer patients at multiple clinical sites. The selected patient populations included, but were not limited to, patients who were treatment naïve, those who had received immunotherapy or adjuvant chemotherapy, and patients who had an exceptional clinical response to treatment and/or disease. Serum antibody binding to a diverse panel of 5 well characterized breast cancer-derived cell lines of luminal and basal sub-types was determined. Utilizing this approach, patients with a robust serological profile across multiple breast cancer cell lines were identified and prioritized for memory B cell repertoire analysis via the I-STAR platform. Using a high throughput and miniaturized, multiplex flow cytometry assay, the secreted IgG antibodies from over 85,000 individually enriched and expanded B cell clones were screened for binding to the tumor cell line panel and a large number of positive B cell clones were identified. The screening hits can be binned into several unique binding profiles, many of which were confirmed to be shared across multiple patient samples. Deep sequence analysis of the variable regions of the antibodies produced by the B cell clones demonstrated that several of the screening hits were derived from clonally related B cells; the majority of the screening hits represented antibodies derived from unique B cell clones. A representative set of these antibodies was expressed recombinantly for further in vitro characterization. Citation Format: Christy Boozer, Paul Algate, Aurelio Bonavia, Mark Branum, Po-Ying Chan-Hui, Alison Fitch, Brad Greenfield, Claire Sutherland, Kristine Swiderek. Discovery of fully human monoclonal antibodies as therapeutic candidates for the treatment of HER2-negative breast cancer [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P2-16-01.