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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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Targeted Cancer Therapies02:57

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The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against...
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Pretargeted Radioimmunotherapy Based on the Inverse Electron Demand Diels-Alder Reaction
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Expression-Dependent Tumor Pretargeting via Engineered Avidity.

Abbigael Harthorn1, Tse-Han Kuo2, Sarah W Torres1

  • 1Department of Biomedical Engineering, University of Minnesota-Twin Cities, Minneapolis, Minnesota 55455, United States.

Molecular Pharmaceutics
|December 20, 2024
PubMed
Summary
This summary is machine-generated.

Engineered a novel binding platform for cancer therapy that uses avidity-driven specificity for precise tumor targeting, improving selectivity and reducing side effects in pretargeted radioligand therapy.

Keywords:
aviditycarcinoembryonic antigenfolate receptorligandmultivalencytargeting

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Area of Science:

  • Biotechnology
  • Oncology
  • Molecular Engineering

Background:

  • Selective delivery of cancer therapeutics to tumor cells is crucial but limited by the lack of truly specific biomarkers.
  • Non-specific binding to healthy tissues causes on-target, off-tumor toxicity, restricting therapeutic windows.

Purpose of the Study:

  • To engineer an advanced binding platform for expression-dependent tumor targeting, enhancing selectivity in cancer therapy.
  • To develop a system that relies on avidity rather than binary biomarker presence for improved targeting.

Main Methods:

  • Engineered affibodies targeting carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) and folate receptor 1 (FolR1) with varied monomeric affinities.
  • Constructed bispecific, trivalent proteins by tethering affibodies to a nanobody for pretargeted radioligand therapy.
  • Evaluated expression-dependent targeting and selectivity in mixed cell cultures.

Main Results:

  • Achieved expression-dependent targeting with affibodies to CEACAM5 (110 nM affinity) and FolR1 (250 nM affinity).
  • Demonstrated over 25-fold differentiation between high and low FolR1-expressing cells using a bispecific, trivalent construct.
  • Developed a size-efficient bivalent molecule with similar selectivity and minimal inhibition by soluble antigen.

Conclusions:

  • Avidity-driven specificity enables precise, expression-dependent tumor targeting, overcoming limitations of traditional biomarker-based approaches.
  • The engineered platform offers enhanced selectivity and reduced susceptibility to soluble antigen interference for improved cancer therapeutics.
  • This work provides new design principles for advanced tumor targeting strategies in pretargeted radioligand therapy.