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Related Concept Videos

T Cell Activation and Clonal Selection01:22

T Cell Activation and Clonal Selection

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...
B Cell Activation and Differentiation01:24

B Cell Activation and Differentiation

The adaptive immune response, a sophisticated defense mechanism, relies on the activation and differentiation of B lymphocytes, or B cells. These processes enable our bodies to mount a tailored response against specific pathogens such as bacteria, free virus particles, toxins, and parasites.
When naive B cells encounter a specific antigen that can bind to the B cell receptor (BCR) on their surface, they undergo sensitization to respond to the antigen's presence. Sensitization begins with...

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Related Experiment Video

Updated: Jun 6, 2026

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

Designing T-cell Engagers: Trade-offs Between Activity and Safety.

Yue Zhang1,2, Mengmeng Wei2,3, Ying Shen1,2

  • 1State Key Laboratory of Advanced Drug Delivery and Release Systems & Innovation Institute for Artificial Intelligence in Medicine, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.

Protein & Cell
|June 5, 2026
PubMed
Summary
This summary is machine-generated.

T-cell engagers (TCEs) show promise but face safety challenges in solid tumors. This review systematically analyzes TCE design strategies to balance antitumor activity and safety for improved immunotherapeutics.

Keywords:
T-cell engageractivitybispecific antibodyimmunotherapymolecular designsafety

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Area of Science:

  • Immunology
  • Oncology
  • Pharmacology

Background:

  • T-cell engagers (TCEs) are potent immunotherapeutics with significant clinical efficacy in various cancers.
  • Balancing the antitumor activity and safety profile of TCEs, especially in solid tumors, remains a critical challenge.
  • Current molecular design strategies often optimize activity and toxicity independently, limiting therapeutic potential.

Purpose of the Study:

  • To systematically analyze principal TCE design strategies, evaluating their strengths, limitations, and interdependencies.
  • To provide a holistic framework for navigating the activity-safety trade-off in TCE development.
  • To guide the development of next-generation TCEs by integrating mechanistic insights.

Main Methods:

  • Categorization of TCE strategies into T-cell interface and tumor cell-directed approaches.
  • Review of T-cell focused strategies: anti-CD3 affinity tuning, costimulatory signals, and immunosuppressive pathway blockade.
  • Examination of tumor-focused strategies: antigen selection, binding valency, and tumor microenvironment (TME)-responsive activation.

Main Results:

  • TCE strategies can be broadly classified based on their targeting interface (T-cell or tumor cell).
  • T-cell interface strategies aim for spatiotemporal control of T-cell activation.
  • Tumor cell-directed strategies focus on enhancing tumor-selective cytotoxicity through antigen targeting and TME responsiveness.

Conclusions:

  • Sophisticated TCE formats allow nuanced functional modulation, but deeper mechanistic understanding is crucial.
  • Integrating insights into T-cell activation and TME biology is essential for developing safer and more effective TCEs.
  • A systematic comparison of existing strategies offers a framework for optimizing TCE design and improving therapeutic outcomes.