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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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Tumor Necrosis Factor (TNF), a proinflammatory cytokine, contributes significantly to the inflammation seen in Crohn's disease. It exists as soluble TNF and membrane-bound TNF, with actions mediated through TNF receptors (TNFR). TNFR activation leads to the release of proinflammatory cytokines, T-cell activation, collagen production, and leukocyte migration, all contributing to inflammation in Crohn's disease. Anti-TNF monoclonal antibodies, namely infliximab (Remicade), adalimumab...
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Therapeutic options for CTLA-4 insufficiency.

David Egg1, Ina Caroline Rump1, Noriko Mitsuiki1

  • 1Institute for Immunodeficiency, Center for Chronic Immunodeficiency, Medical Center, Faculty of Medicine, Albert Ludwig University of Freiburg, Freiburg, Germany.

The Journal of Allergy and Clinical Immunology
|June 10, 2021
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Summary

Germline mutations in cytotoxic T-lymphocyte-associated antigen-4 (CTLA4) cause immune dysregulation. Stem cell transplantation offers a potential cure, while other therapies provide partial control for CTLA4 insufficiency.

Keywords:
CTLA-4HSCTLRBAabataceptcommon variable immunodeficiencydiagnosisprimary immunodeficiencyrituximabsirolimustreatment

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Area of Science:

  • Immunology
  • Genetics
  • Oncology

Background:

  • Germline mutations in cytotoxic T-lymphocyte-associated antigen-4 (CTLA4) impair regulatory T cell function.
  • CTLA4 insufficiency leads to severe autoimmune and lymphoproliferative disorders.
  • Current therapeutic options for CTLA4 insufficiency have variable effectiveness.

Purpose of the Study:

  • To characterize patient responses to specific therapies for CTLA4 insufficiency.
  • To develop organ-specific recommendations for diagnosis and treatment.
  • To analyze clinical features and treatment outcomes in a large cohort.

Main Methods:

  • Retrospective review of clinical data from 173 CTLA4 mutation carriers (2014-2020).
  • Analysis of organ-specific manifestations, medication use, and treatment response.
  • Evaluation of outcomes for various treatments, including stem cell transplantation.

Main Results:

  • 71% of patients received treatment for immune complications.
  • Abatacept, rituximab, sirolimus, and corticosteroids improved disease severity in various organ involvements.
  • Allogeneic hematopoietic stem cell transplantation achieved cure in 72% of patients.

Conclusions:

  • Systemic immunosuppressants and abatacept offer partial, ongoing disease control.
  • Allogeneic hematopoietic stem cell transplantation represents a potential cure for CTLA4 insufficiency.
  • Organ-specific treatment pathways were developed based on study findings.