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Related Concept Videos

Diversity of Antigen Receptors01:28

Diversity of Antigen Receptors

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Antigen receptors are essential components of the immune system crucial in defending the body against foreign invaders. These receptors are present on the surface of B and T cells, enabling them to recognize antigens and mount an appropriate immune response.
Before encountering any antigen, lymphocytes express these receptors. On B cells, the antigen receptor is a membrane-bound antibody molecule called BCR; on T cells, it is a T cell receptor or TCR. B and T cell receptors are composed of two...
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Extraction of Tissue Antigens for Functional Assays
08:32

Extraction of Tissue Antigens for Functional Assays

Published on: September 10, 2012

Prosthetic Antigen Receptors.

Jingjing Shen1, Daniel A Vallera1, Carston R Wagner1

  • 1†Departments of Medicinal Chemistry and ‡Therapeutic Radiology, University of Minnesota, 2231 Sixth Street SE, Minneapolis, Minnesota 55455, United States.

Journal of the American Chemical Society
|August 1, 2015
PubMed
Summary
This summary is machine-generated.

Chemically self-assembled nanorings (CSANs) offer a novel approach to cancer immunotherapy, acting as prosthetic antigen receptors. These bispecific CSANs target both T-cells and malignant B cells, triggering an immune response while allowing for safe, drug-induced disassembly.

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Area of Science:

  • Immunology
  • Biotechnology
  • Oncology

Background:

  • Chimeric antigen receptors (CARs) show promise for cancer immunotherapy but face production and safety challenges due to genetic T-cell engineering.
  • Existing CAR T-cell therapies require complex genetic modification of patient T-cells, posing significant hurdles in manufacturing and safety protocols.

Purpose of the Study:

  • To develop a novel, non-genetically engineered prosthetic antigen receptor system for cancer immunotherapy.
  • To evaluate the efficacy and safety of chemically self-assembled nanorings (CSANs) as bispecific binders for T-cell engagement and cancer cell targeting.

Main Methods:

  • Chemically self-assembled nanorings (CSANs) were engineered to display single-chain antibodies targeting the CD3 ε subunit on T-cells and the CD22 antigen on malignant B cells.
  • The binding stability of antiCD3/antiCD22 CSANs on T-cell surfaces was assessed over time.
  • The disassembly of CSANs from the cell membrane using trimethoprim was demonstrated.
  • T-cell activation markers (IL-2, IFN-γ production) and cytotoxicity were measured in the presence of CD22+ cancer cells.

Main Results:

  • AntiCD3/antiCD22 CSANs demonstrated stable binding to T-cell surfaces for over 4 days.
  • CSANs could be effectively and safely disassembled from T-cells using trimethoprim.
  • T-cells modified with CSANs showed selective IL-2 and IFN-γ production and initiated cytotoxicity against CD22+ B cells.

Conclusions:

  • Bispecific CSANs represent a promising, non-genetically engineered alternative to CARs for cancer immunotherapy.
  • CSANs offer a potentially safer and more readily producible platform for engaging T-cells against B-cell malignancies.
  • The trimethoprim-inducible disassembly mechanism provides a controllable safety feature for this prosthetic antigen receptor system.