Secretion responsive Hydrogels for Identification of Functional single T cells (SHIFT)

Information

  • Research Project
  • 10272884
  • ApplicationId
    10272884
  • Core Project Number
    R21CA251027
  • Full Project Number
    1R21CA251027-01A1
  • Serial Number
    251027
  • FOA Number
    RFA-CA-20-017
  • Sub Project Id
  • Project Start Date
    9/16/2021 - 2 years ago
  • Project End Date
    8/31/2024 - 5 months from now
  • Program Officer Name
    AMIN, ANOWARUL
  • Budget Start Date
    9/16/2021 - 2 years ago
  • Budget End Date
    8/31/2022 - a year ago
  • Fiscal Year
    2021
  • Support Year
    01
  • Suffix
    A1
  • Award Notice Date
    9/16/2021 - 2 years ago
Organizations

Secretion responsive Hydrogels for Identification of Functional single T cells (SHIFT)

Project Summary/Abstract Adoptive cell therapy has the potential to circumvent cancer immune evasion by employing patient-derived, tumor-specific cytotoxic T-cells to attack cancer. While promising responses of advanced cases to cancer immunotherapy bolster the optimism surrounding these therapeutic strategies, interpatient variations in treatment responses demand a new method to select highly effective tumor-specific cytotoxic T-cells for better and safe immunotherapy. We propose a high-throughput, single-cell level method for identifying and recovering highly functional T cells that secrete tumor-killing signals in the presence of tumors. Our proposed technology builds on transformational advances in the generation of droplet emulsions, secretomics, and new hydrogel-based sensing techniques we recently developed. In this assay, tumor-killing T cells and cancer cells will be encapsulated in pairs in a uniformly sized, secreted factor-sensitive hydrogel droplet using a microfluidic droplet generator. The resulting isolated reaction compartments for each cell pair will prevent the mixing of T cells' multiple secreted factors and will concentrate them to allow sensitive detection. The hydrogel will respond to a factor secreted by functional T cells via a dramatic size change, allowing hydrogels with active T cells to be reliably isolated from the heterogeneous mixture using a hydrodynamic size-based particle sorting mechanism. The sorted pairs will be individually recovered using an aspiration pipette and the hydrogel shell dissolved without cell damage, allowing for the recovery of functional individual T cells. We propose to use this high-throughput assay, capable of screening millions of T cells, to identify tumor-responsive T cells and to recover them for downstream analysis or proliferation. This assay is simple, sensitive, and versatile enough to be used by a wide research community or eventually within clinical settings for isolating and profiling rare cells with target secretory phenotypes.

IC Name
NATIONAL CANCER INSTITUTE
  • Activity
    R21
  • Administering IC
    CA
  • Application Type
    1
  • Direct Cost Amount
    136694
  • Indirect Cost Amount
    78451
  • Total Cost
    215145
  • Sub Project Total Cost
  • ARRA Funded
    False
  • CFDA Code
    396
  • Ed Inst. Type
    UNIVERSITY-WIDE
  • Funding ICs
    NCI:215145\
  • Funding Mechanism
    Non-SBIR/STTR RPGs
  • Study Section
    ZCA1
  • Study Section Name
    Special Emphasis Panel
  • Organization Name
    JOHNS HOPKINS UNIVERSITY
  • Organization Department
    MISCELLANEOUS
  • Organization DUNS
    001910777
  • Organization City
    BALTIMORE
  • Organization State
    MD
  • Organization Country
    UNITED STATES
  • Organization Zip Code
    212182680
  • Organization District
    UNITED STATES