Antigen-Screening System - Perfecting the Promise of T Cell Therapies for Infectious Disease & Cancer
Flechtner, JB (2016) Drug Development & Delivery epub June 2016
This article describes Genocea’s proprietary ATLASTM technology, illustrating how finding the RIGHT targets of T cell responses matters for successful immunotherapies and vaccines. The article describes how ATLAS had yielded an HSV-2 immunotherapy that has shown unprecedented efficacy in Phase 2 clinical trials and then introduces emerging cancer immunotherapy programs that highlight the ways ATLAS is poised to revolutionize immuno-oncology.
Grubaugh, D et al. (2013) Vaccine epub Jun 24
This review article provides a concise summary of conventional and emerging methods for identifying protein targets of T cell responses for inclusion in vaccines or diagnostics. This provides context for appreciating the unique benefits of the ATLAS™ platform.
Flechtner, JB (2010) Human Vaccines 6:9, 684-688
In this profile, Jessica Flechtner, the Vice President of Research discusses how Genocea Biosciences was formed, the strength of the technology that facilitates rapid identification of T cell antigens from screens of diverse human subjects, and the company’s business philosophy.
Escherichia coli expressing recombinant antigen and listeriolysin O stimulate class I-restricted CD8+ T cells following uptake by human APC
Hu, PQ et al. (2004) J Immunol 172(3): 1595-601
This article presents the first evidence that E. coli expressing cLLO can be used as antigen delivery vectors in human cultures in vitro, demonstrating an essential element of the ATLAS™ platform functionality. The key message from the article is that E. coli can be engineered to direct antigens to the cytosol of human antigen presenting cells for processing. The article goes on to show that antigen presentation after E. coli uptake and cLLO-mediated release is a function of the proteasome since antigen expression was blockable by proteasome inhibitors but not lysosomal inhibitors.
A recombinant E. coli vaccine to promote MHC class I-dependent antigen presentation: application to cancer immunotherapy
Radford, KJ et al. (2002) Gene Ther 9(21): 1455-63
The focus of this article is the potential for E. coli expressing cLLO to deliver antigens for tumor immunotherapy in mice. Using a model antigen (OVA), the article shows that murine DC, pulsed with E. coli/cLLO/OVA, have an MHC class I epitope presented on their surface, but if the cLLO is not present, the dominant MHC class II epitope is presented. The article goes on to show that E. coli/cLLO/OVA-pulsed DC injected in vivo induce cytotoxic T lymphocytes that can lyse a melanoma cell line that expresses OVA and suppress tumor growth following in vivo challenge. Moreover, they found that the protective immune response is potentiated by simply immunizing the mice with E. coli/cLLO/OVA, which can be either alive or paraformaldehyde fixed. This article provides confirmation that E. coli expressing cLLO and protein antigens are competent at delivering protein antigens for MHC class I presentation resulting in CD8+ T cell responses both in vivo and in vitro, confirming the biological relevance of the system for antigen discovery.
Higgins, DE et al. (1999) Mol Microbiol 31(6): 1631-41
This article from the laboratory of the scientific co-founder of Genocea Biosciences introduces an essential component of the ATLAS™ platform: the cytoplasmic form of listeriolysin O (cLLO), which has been modified so that it can no longer be secreted. This is the first report that E. coli expressing cLLO can deliver co-expressed protein to the cytosol of mouse macrophages. The article demonstrates that the kinetics of antigen delivery to the cytosol is rapid, with proteins available within minutes of phagocytosis. Finally, the paper reports that the efficiency of antigen presentation with this method is much greater compared to E. coli expressing the antigen without cLLO, by a factor of about four logs.