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Related Concept Videos

T Cell Activation and Clonal Selection01:22

T Cell Activation and Clonal Selection

806
T cells are integral to our adaptive immune system, recognizing and effectively responding to foreign antigens. T cell activation and clonal selection are pivotal in orchestrating this immune response. This article elucidates these mechanisms, detailing the roles of cluster of differentiation (CD) markers, major histocompatibility complex (MHC) molecules, costimulatory signals, and the process of clonal selection.
Naive T cells that have not yet encountered an antigen express two primary CD...
806
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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Conservative Site-specific Recombination and Phase Variation02:53

Conservative Site-specific Recombination and Phase Variation

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Because the DNA segments are cut and reorganized in a direction-specific manner, site-specific recombination has emerged as an efficient genetic engineering technique. Flippase and Cyclization recombinases or Flp and Cre, respectively, are two members of the tyrosine recombinase family derived from bacteriophages, that are used to mediate site-specific DNA insertions, deletions, and targeted expression of proteins in mammalian cell lines.
The recognition sites for Cre recombinase called LoxP...
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Related Experiment Video

Updated: Jul 19, 2025

Non-Viral Engineering of Primary Human T Cells via Homology-Mediated End-Joining Targeted Integration of Large DNA Templates
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Non-Viral Engineering of Primary Human T Cells via Homology-Mediated End-Joining Targeted Integration of Large DNA Templates

Published on: May 9, 2025

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Programmable multispecific DNA-origami-based T-cell engagers.

Klaus F Wagenbauer1,2, Nhi Pham1,2, Adrian Gottschlich3,4

  • 1Department of Biosciences, School of Natural Sciences, Technical University of Munich, Garching, Germany.

Nature Nanotechnology
|August 17, 2023
PubMed
Summary
This summary is machine-generated.

Researchers developed a modular DNA origami platform for rapidly designing and testing multispecific antibodies. This approach accelerates the discovery and preclinical development of novel antibody therapeutics for cancer treatment.

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Area of Science:

  • Biotechnology and Nanotechnology
  • Immunology and Cancer Therapeutics

Background:

  • Multispecific antibodies are valuable therapeutic agents, but their design and assembly require optimization.
  • Current methods for developing these complex biologics can be time-consuming and inefficient.

Purpose of the Study:

  • To establish a modular and programmable platform for assembling multispecific antibodies.
  • To rapidly generate, screen, and validate antibody variants for therapeutic applications.

Main Methods:

  • Utilized DNA origami nanocarriers for the modular assembly of IgG antibodies, F(ab), and scFv fragments.
  • Screened 105 distinct quadruplet antibody variants for T-cell activation in the presence of target cells.
  • Evaluated T-cell engagers in vitro for T-cell-mediated lysis of cancer cell lines and in vivo in a xenograft mouse model.

Main Results:

  • Identified novel T-cell engagers capable of specific and efficient T-cell-mediated lysis of five distinct target cell lines in vitro.
  • Demonstrated in vivo efficacy of these T-cell engagers in targeting and lysing tumor cells in a mouse model.
  • Validated the platform's ability to rapidly generate and test multispecific antibodies.

Conclusions:

  • The DNA origami-based modular assembly approach significantly accelerates the generation and preclinical testing of multispecific antibodies.
  • This platform facilitates the transition from in vitro discovery to in vivo proof of concept for antibody therapeutics.
  • Enables rapid development of bispecific and multispecific antibodies for diverse therapeutic applications, particularly in oncology.