Abstract A61: Engineered antigen presenting T cells for treatment of solid tumor cancers

• Published in: Cancer immunology research 2018-09, Vol.6 (9_Supplement), p.A61-A61
• Main Authors: Talarico, LeeAnn, Vicente-Suarez, Ildefonso, Blagovic, Katarina, Chong-Ng, Eritza, Jones, Lauren, Pomerance, Lucas, Bernstein, Howard
• Format: Article
• Language: English
• ISSN: 2326-6066; 2326-6074
• DOI: 10.1158/2326-6074.TUMIMM17-A61

Ex vivo manipulation of primary cells has shown immense clinical potential with the advent of adoptive T cell therapies to stimulate CD8 cytotoxic T lymphocyte (CTL) responses for the treatment of cancer. CTLs stimulated by tumor-associated antigens can target and clear solid tumors, however ex vivo manipulation methods for adoptive T cell transfer can be prohibitively time intensive. SQZ’s approach harnesses the endogenous T cell expansion mechanisms stimulated by antigen presentation to produce a relevant CTL dose. Previous efforts using antigen presenting cells (APCs) to induce this response have failed due to the difficulty inherent in delivering antigen to the APC cytosol, a necessary step for CTL activation. Within an APC, antigen location in the cytosol or endosome dictates how antigens are processed, presented, and the resultant adaptive immune system reaction. For an effective CTL response the antigens must be presented on MHC class I (MHC-I) molecules, which only occurs for antigens located in the cytosol. Antigen delivery methods, such as endocytosis, electroporation, and nanoparticle-based systems, can result in low efficiency, accumulation of material in endosomal compartments, cytotoxicity, and/or off-target effects. Furthermore, these processes are not amenable to scalable deployment, limiting the number of patients able to be treated. To circumvent such issues, we can achieve direct delivery of antigens into the APC cytosol with CellSqueeze®, resulting in MHC-I antigen presentation and effective stimulation of CTL activity. CellSqueeze® is a vector-free microfluidic platform that causes temporary membrane disruption by rapid mechanical deformation, enabling delivery of cell-engineering materials to diffuse into the cytosol without disrupting normal cell function. The CellSqueeze® platform, developed at MIT, has demonstrated efficacious delivery of various challenging materials, such as peptides and proteins, to patient-derived cells including stem cells and primary immune cells. We are developing our platform to employ primary human T cells as APCs. Previous CTL stimulation efforts have attempted to deliver antigenic material to dendritic cells (DCs); however, they are much less numerous in the blood and differentiation from monocytes is time consuming. This work uses primary human T cells, which are highly abundant in the blood, as APCs. We have demonstrated that delivery of antigenic material to T cells with the CellSqueeze® technology ef