CD8 T cells are critical to immunotherapeutic intervention in cancer. However, the ability to efficiently target antigens for MHC-I presentation has limited the efficacy of immunization strategies. Here, we use microfluidics-based SQZ cell therapy platform to deliver antigen to the cytosol of target APCs, resulting in enhanced presentation on MHC-I. Given that no expansion time is required to engineer these APCs, this approach allows for rapid manufacturing of billions of non-conventional APCs capable of priming CD8+ T cell responses.
Protein and peptide antigens were delivered to murine or human T cells with the SQZ cell therapy platform. The response to in vivo immunization of C57BL/6 mice was assessed by flow cytometry. Tumor experiments were conducted with the TC-1 cell line. Human T cells were co-cultured with epitope-reactive human responder CD8+ T cells, and interferon gamma production was quantified to assess antigen-specific responses.
In murine systems, we demonstrate that therapeutic immunization with T cells loaded with E7 using the SQZ platform are capable of eliciting strong anti-tumor effects. These anti-tumor responses correlate with an increase in antigen-specific CD8+ tumor infiltrating lymphocytes that is dependent on the co-administration of an adjuvant. In human cells, we demonstrate that primary T cells loaded with CMV and HPV16 antigens using SQZ can stimulate antigen-specific CD8+ T cell responses in vitro. Importantly, delivery to T cells scales from millions up to billions of cells per minute and antigen presentation is retained even after cryo-preservation.
Through the direct cytosolic delivery of antigen, the SQZ cell therapy platform enables the use of T cells, a readily accessible and abundant cell type, to function as APCs for immunization. This strategy has demonstrated the ability to generate CD8+ T cell responses in both murine and human systems and has been scaled up for clinical implementation. With the ease and speed of manufacturing, these results have the potential to translate into a cellular immune therapy for oncology patients.
Clinical trial identification
Legal entity responsible for the study
S.M. Loughhead, M.G. Booty, K. Hlavaty, A. Vicente-Suarez, K. Blagovic, M. Myint, B. Stokes, D. Yarar, H. Bernstein, A. Sharei: Employee of SQZ Biotech.