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Related Concept Videos

Targeted Cancer Therapies02:57

Targeted Cancer Therapies

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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.
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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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Related Experiment Video

Updated: Jun 15, 2025

Identifying PD-1/PD-L1 Inhibitors with Surface Plasmon Resonance Technology
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Targeted CD47 checkpoint blockade using a mesothelin-directed antibody construct for enhanced solid tumor-specific

Anna Reischer1,2, Alexandra Leutbecher1,2, Björn Hiller3

  • 1Department of Medicine III, University Hospital, LMU Munich, Munich, Germany.

Cancer Immunology, Immunotherapy : CII
|May 22, 2025
PubMed
Summary

This study developed a novel antibody construct to block the CD47 immune checkpoint in cancer. The new therapy targets tumors specifically, reducing toxic side effects seen with other CD47 blockers.

Keywords:
CD47–SIRPαInnate immune checkpointsMesothelinMultifunctional antibodiesSolid tumors

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Area of Science:

  • Immunology
  • Oncology
  • Biotechnology

Background:

  • CD47 is a key immune checkpoint upregulated in many cancers, enabling immune evasion by signaling 'don't eat me' via SIRPα.
  • Blocking the CD47-SIRPα axis is a promising cancer immunotherapy, but faces challenges like on-target off-leukemia toxicity and antigen sink effects.

Purpose of the Study:

  • To develop a multifunctional antibody construct combining low-affinity CD47 blockade with tumor-specific targeting to mitigate CD47-related toxicities.
  • To evaluate the efficacy and safety of a novel antibody, SIRPα-αMSLN LicMAb, in preclinical cancer models.

Main Methods:

  • Created a local inhibitory checkpoint monoclonal antibody (LicMAb) by fusing SIRPα domains to an anti-mesothelin (MSLN) antibody.
  • Assessed tumor-specific binding, CD47 blocking, and immune responses (ADCC, ADCP) in epithelial ovarian cancer (EOC) and pancreatic ductal adenocarcinoma (PDAC) models.

Main Results:

  • SIRPα-αMSLN LicMAb demonstrated tumor-specific binding and CD47 blockade, even with healthy cells present.
  • The LicMAb induced NK-cell-mediated cytotoxicity and enhanced phagocytosis of EOC and PDAC cells.
  • Specifically driven cell death was observed in EOC organoids, confirming tumor-restricted activity.

Conclusions:

  • The SIRPα-αMSLN LicMAb effectively blocks the CD47-SIRPα axis in a tumor-restricted manner.
  • This approach shows potential for treating solid tumors by combining specific antitumor responses with reduced off-tumor toxicities.