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Prevention of organ allograft rejection by a specific Janus kinase 3 inhibitor

Paul S Changelian1, Mark E Flanagan, Douglas J Ball

  • 1Immunology Group, Department of Antibacterials and Immunology, Pfizer Global Researchand Development, Groton, CT 06340, USA. paul_s_changelian@groton.pfizer.com

Science (New York, N.Y.)
|November 1, 2003
PubMed

Insights

Janus kinase 3 (JAK3) inhibition with CP-690,550 shows promise for immunosuppression. This JAK3 inhibitor prolonged transplant survival in preclinical models without adverse effects, suggesting potential for human organ transplantation.

Area of Science:

  • Immunology
  • Pharmacology
  • Transplantation Science

Background:

  • Janus kinase 3 (JAK3) is crucial for cytokine signaling, making it a key target for immunosuppression.
  • JAK3 plays a vital role in immune responses relevant to transplantation.

Purpose of the Study:

  • To develop and evaluate a specific, orally active inhibitor of JAK3, named CP-690,550.
  • To assess the efficacy and safety of CP-690,550 in preclinical transplantation models.

Main Methods:

  • Development of a selective JAK3 inhibitor, CP-690,550.
  • Evaluation of CP-690,550 in a murine heart transplantation model.
  • Assessment of CP-690,550 in kidney transplantation models in cynomolgus monkeys.

Main Results:

  • CP-690,550 significantly prolonged survival in both murine heart and primate kidney transplant models.
  • Treatment with CP-690,550 did not lead to hypertension, hyperlipidemia, or lymphoproliferative disease.
  • The drug demonstrated a favorable safety profile in preclinical studies.

Conclusions:

  • JAK3 blockade with CP-690,550 offers a potential therapeutic strategy for immunosuppression in organ transplantation.
  • CP-690,550 exhibits potential for broader clinical applications requiring immunosuppression.

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