Recombinant CD40-ligand

Summary

Recombinant CD40-ligand (rCD40L, also known as recombinant CD154 or rCD154) is a recombinant form of the endogenous CD40L (CD154) protein, a member of the TNF superfamily. It has been investigated as an immunotherapeutic agent in oncology, immunodeficiency states (particularly X-linked hyper-IgM syndrome), and as an immune adjuvant. Clinical development was hampered by thromboembolic adverse events observed in early trials, leading to suspension of most programs.

Mechanism of Action

Binds to CD40 receptor on B cells, dendritic cells, monocytes, and other antigen-presenting cells, activating NF-κB and MAPK signaling pathways, thereby promoting B cell proliferation, immunoglobulin class switching, dendritic cell maturation, and T cell co-stimulation.

Routes of Administration

Goals & Uses

• Vaccine adjuvantVaccinologyLow
• Platelet activation researchHematology / ResearchModerate
• Cancer immunotherapyOncologyLow
• B cell immunodeficiency (Hyper-IgM syndrome)Immunology / Rare DiseaseLow

Contraindications

• History of thromboembolic eventsHematologicalHigh
• Severe cardiovascular diseaseCardiovascularHigh
• Active autoimmune diseaseAutoimmunityModerate

Adverse Effects

• Thromboembolic events (DVT, PE, arterial thrombosis)Hematological / VascularUncommon
• Injection site reactionsLocalCommon
• Fever / flu-like symptomsSystemicCommon
• Anti-drug antibody formationImmunologicalUncommon
• Cytokine release / inflammatory responseImmunologicalUncommon

Drug Interactions

• Antiplatelet agents (aspirin, clopidogrel)Low
• Immunosuppressive agents (e.g., corticosteroids, cyclosporine)Moderate
• Anticoagulants (warfarin, heparin, direct oral anticoagulants)Moderate

Population Constraints

• Pediatric patientsAgeRelative
• Patients with hypercoagulable statesHematologicalAbsolute
• Pregnant or breastfeeding womenReproductiveAbsolute
• Elderly patientsAgeRelative

Regulatory Status

• European UnionInvestigationalNo EMA approval. Limited early-phase European trials; development largely discontinued for systemic administration.
• United StatesInvestigationalNo FDA-approved indication. IND-stage trials were conducted but most programs were suspended due to thromboembolic adverse events.
• United KingdomInvestigationalNo MHRA approval. Follows similar status to EU; no approved therapeutic use.

No approved indication in any major jurisdiction. Early-phase clinical trials were halted or suspended due to serious thromboembolic events. Remains primarily a research-stage molecule. Some investigational use continues in ex vivo settings and as a vaccine adjuvant component.

Evidence & Sources

No sources recorded yet.