Unbiased Profiling of the Immunomodulatory Properties of Soluble Proteins

摘要: The function of the innate and adaptive immune system is tightly controlled by soluble signals such as cytokines on one hand cell-cell interactions other. Immunotherapeutics modulate these signaling axes to direct human against malignant cells are promising revolutionize way how we treat cancer. Yet, not all malignancies respond equally well existing immunotherapy new targets required. Here use a novel high content imaging method compatible with PBMCs (Vladimer, Snijder et al., Nat. Chem. Biol. 2017) systematically quantify physical interaction patterns between CD3, CD4, CD8, CD11c, CD14, CD19 CD56 positive in response perturbation 90 cell-surface receptors ex vivo . Whilst there many tools measure other immunoregulatory factors throughput (e.g., alpha screen), potentially multiplexed fashion cytokine bead arrays), systematic measurement high-throughput has so far been elusive. We were able identify specific changes that could be reproduced over different donors treatment protein or small molecule perturbations. hypothesise unknown immunomodulatory functions can inferred comparison induced molecules known properties. Further, coregulation analysis pairs map out cell contact dependent regulatory circuits an unbiased manner. Overall, our promises become valuable tool for study phenotypic discovery desired An overview preliminary results will presented. Disclosures Krall: Allcyte Gmbh: Equity Ownership. Vladimer: Snijder: Allcyte: Ownership, Other: founder shareholder GmbH holds worldwide exclusive license commercializes Pharmacoscopy technology.. Superti-Furga: GmbH: