Drug intelligence / Profile preview

cyclophosphamide + abatacept + tacrolimus

Development stage
Unknown
Lead developer
NYU Langone Health
Modality
Small Molecules
Administration
Intravenous, Oral
01

Overview

The combination of cyclophosphamide, abatacept, and tacrolimus—sometimes referred to as the CAST regimen—is an investigational immunosuppressive protocol primarily studied for the prevention of graft-versus-host disease (GVHD) following allogeneic hematopoietic stem cell transplantation (HSCT), especially in haploidentical or mismatched donor settings. Cyclophosphamide is a cytotoxic alkylating agent that induces apoptosis in activated T cells post-transplant. Abatacept is a fusion protein (CTLA4-Ig) that blocks T-cell activation by inhibiting CD28-mediated costimulation through binding to CD80/CD86 on antigen-presenting cells. Tacrolimus is a calcineurin inhibitor that suppresses T-cell activation by inhibiting interleukin-2 transcription. Together, these agents act synergistically to reduce the incidence and severity of acute GVHD while maintaining engraftment and minimizing relapse risk[2][6][7]. The regimen has shown promising safety and efficacy results in phase 1b/2 clinical trials for GVHD prophylaxis after peripheral blood haploidentical HSCT[2].

Other names
CAST regimen
02

Targets

FKBP1ACD80 (T-lymphocyte activation antigen CD80)CD86 (T-lymphocyte activation antigen CD86)DNACN (Calcineurin)

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