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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 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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Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
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Endoglin-Directed CAR T Cells Comprehensively Target Tumors in Advanced Sarcomas.

Harrison R Berger1,2,3, Malina Maharana1,2,3, Jeneffer Mirabal1,2,3

  • 1Center for Cell and Gene Therapy, Baylor College of Medicine, Houston Methodist Hospital, Texas Children's Hospital, Houston, Texas.

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Chimeric antigen receptor T cell (CAR-T) therapy shows promise for advanced sarcomas. Researchers developed endoglin (ENG)-targeted CAR-T cells that effectively target sarcoma cells and inhibit tumor growth and metastasis.

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Area of Science:

  • Oncology
  • Immunotherapy
  • Cellular Therapy

Background:

  • Advanced sarcomas have poor prognoses and limited treatment options.
  • Effective therapeutic targets for chimeric antigen receptor T cell (CAR-T) therapy in sarcomas are scarce.
  • Endoglin (ENG/CD105), a TGF-β co-receptor, was identified as a potential target due to its expression on sarcomas and its role in invasiveness.

Purpose of the Study:

  • To develop and evaluate a novel human endoglin (ENG)-targeted CAR-T cell therapy for advanced sarcomas.
  • To assess the efficacy of ENG CAR-T cells against various sarcoma cell lines and in preclinical sarcoma models.

Main Methods:

  • Designed and generated a second-generation human ENG-targeting CAR molecule.
  • Retrovirally transduced primary human T cells to create ENG CAR-T cells.
  • Evaluated ENG CAR-T cell function in vitro (cytokine release, proliferation, cytotoxicity) and in vivo (orthotopic murine sarcoma models).

Main Results:

  • ENG CAR-T cells demonstrated antigen-specific cytokine release, robust proliferation, memory formation, and potent cytotoxic activity against sarcoma cell lines.
  • ENG CAR-T cells effectively disrupted multicellular tumor spheroids and overcame cancer-associated fibroblast barriers in vitro.
  • In vivo studies showed ENG CAR-T treatment controlled tumor growth, reduced metastasis, and extended survival in murine sarcoma models.

Conclusions:

  • Endoglin (ENG) plays a role in sarcoma metastasis.
  • Human ENG CAR-T cells are a promising potential therapy for advanced sarcomas, addressing key challenges like tumor compactness and stromal barriers.