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Targeting cytokines and immune checkpoints in atherosclerosis with monoclonal antibodies

Esther Lutgens1, Jeremie Joffre2, Bram van Os3

  • 1Department of Medical Biochemistry Experimental Vascular Biology, Amsterdam, the Netherlands; Institute for Cardiovascular Prevention (IPEK), Ludwig-Maximilians-Universität, Pettenkoferstraße 8a & 9, 80336, Munich, Germany; German Centre for Cardiovascular Research (DZHK), Partner Site Munich Heart Alliance, Pettenkoferstraße 8a & 9, 80336, Munich, Germany.

Atherosclerosis
|October 1, 2021
PubMed

Insights

Monoclonal antibodies targeting cytokines show promise in reducing cardiovascular risk for inflammatory diseases. However, careful consideration of specific treatments and patient conditions is crucial for managing athero-thrombotic events.

Area of Science:

  • Immunology
  • Cardiology
  • Pharmacology

Background:

  • Chronic inflammatory diseases like rheumatoid arthritis and psoriasis are linked to increased cardiovascular risk.
  • Cytokines play a significant role in the development of atherosclerosis, a key factor in cardiovascular disease.
  • Monoclonal antibodies targeting specific cytokines have emerged as treatments for these inflammatory conditions.

Purpose of the Study:

  • To evaluate the cardiovascular impact of cytokine-targeting therapies in chronic inflammatory diseases.
  • To assess the role of immunomodulatory treatments in managing athero-thrombotic cardiovascular risk.
  • To explore the future implications for cardiologists in managing patients with inflammatory diseases and cancer.

Main Methods:

  • Review of clinical studies on monoclonal antibodies targeting TNFα, IL-6R, and IL-1β.
  • Analysis of data from trials investigating antibodies against costimulatory molecules (e.g., CD28/CD80/86) and immune checkpoint inhibitors (CTLA-4, PD1, PDL1).
  • Examination of the cardiovascular outcomes in patients with chronic inflammatory diseases and cancer treated with these immunomodulatory agents.

Main Results:

  • Anti-TNFα and anti-IL-6R antibodies demonstrated protective effects against athero-thrombotic risk in inflammatory diseases, though anti-TNFα can worsen heart failure.
  • Anti-IL-1β therapy significantly reduced cardiovascular events in coronary artery disease patients (CANTOS study).
  • Abatacept (anti-CD28/CD80/86) reduced cardiovascular risk, while immune checkpoint inhibitors (anti-CTLA-4, PD1, PDL1) may increase athero-thrombotic risk in cancer patients.

Conclusions:

  • Monoclonal antibody therapies targeting cytokines and costimulatory molecules offer potential benefits for cardiovascular risk in inflammatory conditions.
  • Caution is advised with certain therapies (e.g., anti-TNFα in heart failure) and in specific patient populations (e.g., cancer patients on immune checkpoint inhibitors).
  • Future cardiology practice will involve assessing cardiovascular risk and guiding immunomodulatory treatment choices for patients with inflammatory diseases and cancer.
Keywords:
AntibodyAtherosclerosisCheckpointCytokineInflammation

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