Anti-CD40 [2C10R4] is a recombinant chimeric monoclonal antibody targeting CD40, engineered by fusing the murine 2C10 variable region with constant regions from rhesus IgG4-kappa. This configuration yields a non-cytolytic antagonist optimized for costimulation blockade in nonhuman primate (NHP) models. As a CD40 antagonist, 2C10R4 blocks the CD40-CD154 (CD40L) interaction—a key pathway in T-cell dependent B-cell activation and antigen-presenting cell licensing—without inducing complement activation or FcγR-mediated depletion.

This antibody product was tested across a wide range of transplantation, xenotransplantation, and autoimmunity studies, and is widely cited as the gold-standard CD40 blocking agent in NHP models. An MTA is required for distribution.

Species Reactivity: Tested in African Green monkeys (Chlorocebus spp.), rhesus macaques (M. mulatta), cynomolgus macaques (M. fascicularis), and baboons (Papio spp.)

Representative Applications and Publications

Islet and Kidney Allotransplantation

• Tolerogenic protocols: Induction of long-term tolerance in NHPs receiving islet allografts via apoptotic donor leukocytes + 2C10R4 blockade.
  [Hawthorne et al., Nat Commun 2019, PMID: 31375697] Annotation

• Simultaneous islet–kidney transplantation: 2C10R4 combined with rapamycin supports graft acceptance.
  [Zhou et al., Am J Transplant 2017, PMID: 27501203] Annotation

Xenotransplantation (Pig-to-NHP Models)

• Cardiac Xenografts: Demonstrated critical role of 2C10R4 in prolonging survival of pig heart grafts in NHPs.
  [Mohudin et al., Nat Commun 2016, PMID: 27045379] Annotation

• Kidney and Liver Xenografts: 2C10R4 incorporated in anti-inflammatory regimens, often with IL-6 blockade.
  [Kim et al., Am J Transplant 2018, PMID: 28489305] Annotation

• Maintenance monotherapy: Suggested as sufficient monotherapy in some xenotransplant models.
  [Iacono et al., Xenotransplantation 2021, PMID: 34850468] Annotation

Inflammation & Biomarker Studies

• Predictive biomarkers of graft failure: 2C10R4 used in context of early serum biomarker changes (e.g., SAA).
  [Weiss et al., Int J Surg 2018, PMID: 30521954] Annotation

• Histopathological inflammation readouts: Inflammatory responses were assessed in Neu5Gc-expressing pig kidney grafts.
  [Wen et al., Xenotransplantation 2021, PMID: 34644438] Annotation

Other Organ & Corneal Grafts

• Corneal xenografts: Used to enhance long-term survival of porcine corneal grafts in primates.
  [Bharat et al., Am J Transplant 2018, PMID: 29722120] Annotation

Viral Pathogenesis

• EBV-associated lymphoma models: CD40 blockade employed to assess T cell roles in EBV-induced lymphomagenesis.
  [Cahir-McFarland et al., J Clin Invest 2015, PMID: 25485679] Annotation

Selected Citations