It's popular to use "APC" instead of "dendritic cell" these days.
;-)
HPV is just a tad easier than type 1 diabetes.
>> squeezing a patient's immune cells through narrow channels on a microfluidic chip, making the cell membranes temporarily open up <<
Electroporation has lived forever.
>> when SQZ's technology is used to target autoimmune diseases, red blood cells can be squeezed and manipulated to suppress an immune response, which Sharei says could lead to an innovative approach to treating chronic auto-immune diseases <<
OK, now I'm interested. Thanks for the tickle. CEO is five years out of Ph.D., but he's definitely THE champion of the technique (follow link below abstract).
Proc Natl Acad Sci U S A. 2018 Oct 31. pii: 201809671. doi: 10.1073/pnas.1809671115. [Epub ahead of print]
Cell engineering with microfluidic squeezing preserves functionality of primary immune cells in vivo.
DiTommaso T1, Cole JM2, Cassereau L2, Buggé JA2, Hanson JLS2, Bridgen DT2, Stokes BD2, Loughhead SM2, Beutel BA2, Gilbert JB2, Nussbaum K3, Sorrentino A3, Toggweiler J3, Schmidt T3, Gyuelveszi G3, Bernstein H2, Sharei A2.
1
SQZ Biotechnologies, Watertown, MA 02472; tia.ditommaso@sqzbiotech.com.
2
SQZ Biotechnologies, Watertown, MA 02472.
3
Oncology Discovery Translational Area, Roche Pharma Research and Early Development, Roche Innovation Center Zurich, 8952 Schlieren, Switzerland.
The translational potential of cell-based therapies is often limited by complications related to effectively engineering and manufacturing functional cells. While the use of electroporation is widespread, the impact of electroporation on cell state and function has yet to be fully characterized. Here, we use a genome-wide approach to study optimized electroporation treatment and identify striking disruptions in the expression profiles of key functional transcripts of human T cells. These genetic disruptions result in concomitant perturbation of cytokine secretion including a 648-fold increase in IL-2 secretion (P < 0.01) and a 30-fold increase in IFN-? secretion (P < 0.05). Ultimately, the effects at the transcript and protein level resulted in functional deficiencies in vivo, with electroporated T cells failing to demonstrate sustained antigen-specific effector responses when subjected to immunological challenge. In contrast, cells subjected to a mechanical membrane disruption-based delivery mechanism, cell squeezing, had minimal aberrant transcriptional responses [0% of filtered genes misregulated, false discovery rate (FDR) q < 0.1] relative to electroporation (17% of genes misregulated, FDR q < 0.1) and showed undiminished effector responses, homing capabilities, and therapeutic potential in vivo. In a direct comparison of functionality, T cells edited for PD-1 via electroporation failed to distinguish from untreated controls in a therapeutic tumor model, while T cells edited with similar efficiency via cell squeezing demonstrated the expected tumor-killing advantage. This work demonstrates that the delivery mechanism used to insert biomolecules affects functionality and warrants further study.
ncbi.nlm.nih.gov |
