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Related Concept Videos

Tumor Immunotherapy01:27

Tumor Immunotherapy

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Immunotherapy is a treatment that boosts or manipulates the immune system to fight diseases, including cancer. For instance, by stimulating an immune response through vaccinations against viruses that cause cancers, like hepatitis B virus and human papillomavirus, these diseases can be prevented. Nonetheless, some cancer cells can avoid the immune system due to their rapid mutation and division. The immune response to many cancers involves three phases: elimination, equilibrium, and escape.
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The Tumor Microenvironment02:17

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Every normal cell or tissue is embedded in a complex local environment called stroma, consisting of different cell types, a basal membrane, and blood vessels. As normal cells mutate and develop into cancer cells, their local environment also changes to allow cancer progression. The tumor microenvironment (TME) consists of a complex cellular matrix of stromal cells and the developing tumor. The cross-talk between cancer cells and surrounding stromal cells is critical to disrupt normal tissue...
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Precision-Engineered CD3 T-Cell Engagers for Solid Tumours: Conditional Activation, Microenvironment Modulation, and

Md Zeyaullah1, Abdullah M AlShahrani1, Mohammad Suhail Khan2

  • 1Department of Basic Medical Science, College of Applied Medical Sciences, Khamis Mushayt Campus, King Khalid University (KKU), Abha 62561, Saudi Arabia.

Cancers
|April 14, 2026
PubMed
Summary
This summary is machine-generated.

T-cell-engaging bispecific antibodies (TCEs) show promise in solid tumors, with response rates nearing 40% in select cases. Advances in engineering and patient selection are transforming TCEs into a viable platform therapy for solid tumors.

Keywords:
CD3 T-cell engagerDLL3antigen heterogeneitybispecific antibodycancer immunotherapycytokine-release syndromesmall-cell lung cancertumour microenvironment

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Area of Science:

  • Oncology
  • Immunotherapy
  • Antibody Engineering

Background:

  • T-cell-engaging bispecific antibodies (TCEs) have revolutionized blood cancer treatment but show limited efficacy in solid tumors due to tumor microenvironment and T-cell dysfunction.
  • Solid tumor challenges include antigen heterogeneity, immunosuppressive microenvironments, and T-cell exhaustion, hindering TCE effectiveness.

Purpose of the Study:

  • To review the clinical efficacy and engineering strategies of CD3-based TCEs in solid tumors.
  • To analyze resistance mechanisms and identify future directions for TCE therapy in solid tumors.

Main Methods:

  • Systematic review of 55 Phase I-III trials involving CD3-based TCEs in solid tumors.
  • Analysis of genomic and immunohistochemical data to understand next-generation engineering and resistance mechanisms.

Main Results:

  • Response rates in selected solid tumor settings approach 40%, with significant survival benefits observed for tarlatamab in small-cell lung cancer.
  • Xaluritamig demonstrated ~41% response rates in metastatic castration-resistant prostate cancer.
  • Step-up dosing significantly reduced severe cytokine release syndrome (<1%), allowing for outpatient administration.

Conclusions:

  • Resistance mechanisms include antigen heterogeneity, immunosuppressive tumor microenvironments, and T-cell exhaustion.
  • Next-generation TCE platforms, combined with biomarker selection and TME modulation, represent a transformative strategy.
  • TCEs are poised to become standard-of-care for biomarker-defined solid tumors by 2028-2030.