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carfilzomib + belatacept
- Development stage
- Unknown
- Lead developer
- National Institute of Allergy and Infectious Diseases
- Modality
- Fc-Fusion Proteins → Carrier/Scaffold Proteins → Recombinant Proteins and Enzymes, Small Molecules
- Administration
- Intravenous
01
Overview
This combination therapy, consisting of the proteasome inhibitor carfilzomib (Kyprolis) and the costimulation blocker belatacept (Nulojix), is being investigated for the desensitization of highly sensitized kidney transplant candidates. Carfilzomib is a second-generation small molecule proteasome inhibitor that irreversibly binds to the 20S proteasome, leading to the depletion of antibody-producing plasma cells. Belatacept is a recombinant fusion protein composed of the Fc fragment of human IgG1 linked to the extracellular domain of CTLA-4; it binds to CD80 and CD86 on antigen-presenting cells to block the CD28-mediated T-cell costimulation pathway. This dual-action approach, evaluated in the NIAID-sponsored ADAPT trial (ITN089ST), aims to reduce donor-specific HLA antibodies and inhibit germinal center reactions, thereby increasing the likelihood of compatible transplantation and improving long-term outcomes for patients with high immunological risk.
- Brand names
- Kyprolis + Nulojix
- Other names
- ADAPT regimenCarfilzomib and Belatacept desensitization therapy
02
Targets
26S proteasomeCD80 (T-lymphocyte activation antigen CD80)CD86 (T-lymphocyte activation antigen CD86)
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