| First Author | Booty MG | Year | 2022 |
| Journal | J Immunol | Volume | 208 |
| Issue | 4 | Pages | 929-940 |
| PubMed ID | 35091434 | Mgi Jnum | J:392036 |
| Mgi Id | MGI:7257951 | Doi | 10.4049/jimmunol.2100656 |
| Citation | Booty MG, et al. (2022) Microfluidic Squeezing Enables MHC Class I Antigen Presentation by Diverse Immune Cells to Elicit CD8(+) T Cell Responses with Antitumor Activity. J Immunol 208(4):929-940 |
| abstractText | CD8(+) T cell responses are the foundation of the recent clinical success of immunotherapy in oncologic indications. Although checkpoint inhibitors have enhanced the activity of existing CD8(+) T cell responses, therapeutic approaches to generate Ag-specific CD8(+) T cell responses have had limited success. Here, we demonstrate that cytosolic delivery of Ag through microfluidic squeezing enables MHC class I presentation to CD8(+) T cells by diverse cell types. In murine dendritic cells (DCs), squeezed DCs were approximately 1000-fold more potent at eliciting CD8(+) T cell responses than DCs cross-presenting the same amount of protein Ag. The approach also enabled engineering of less conventional APCs, such as T cells, for effective priming of CD8(+) T cells in vitro and in vivo. Mixtures of immune cells, such as murine splenocytes, also elicited CD8(+) T cell responses in vivo when squeezed with Ag. We demonstrate that squeezing enables effective MHC class I presentation by human DCs, T cells, B cells, and PBMCs and that, in clinical scale formats, the system can squeeze up to 2 billion cells per minute. Using the human papillomavirus 16 (HPV16) murine model, TC-1, we demonstrate that squeezed B cells, T cells, and unfractionated splenocytes elicit antitumor immunity and correlate with an influx of HPV-specific CD8(+) T cells such that >80% of CD8s in the tumor were HPV specific. Together, these findings demonstrate the potential of cytosolic Ag delivery to drive robust CD8(+) T cell responses and illustrate the potential for an autologous cell-based vaccine with minimal turnaround time for patients. |
