# Effects of combining anti-CD40 and anti-CD11b mAb107 on survival of pig kidney xenografts in cynomolgus monkeys

> **NIH NIH R21** · MASSACHUSETTS GENERAL HOSPITAL · 2022 · $242,440

## Abstract

Project Summary/Abstract
Disrupting the CD40-CD154 costimulatory pathway using an anti-CD154-based regimen has markedly improved
gene-edited pig organ xenograft survival in nonhuman primate (NHP) recipients. However, the life-threatening
thromboembolic complications associated with use of anti-CD154 have precluded its approval for human use.
Attempts to avoid this complication by blocking CD40, the classic CD154 receptor, paradoxically impeded rather
than promoted tolerance induction in NHP recipients. A recent study showed that blocking a second CD154
receptor, integrin CD11b, significantly increased efficacy of anti-CD40 in prolonging allograft survival in mice.
Although mouse models are important for developing proof-of-concept, it remains to be determined if combined
blockade of CD40 and CD11b can be extended to prolonging survival of xenografts in NHP recipients, studies that
will be critical for guiding clinical translation. In preliminary studies, we show that an anti-CD11b mAb with a unique
mechanism of action not only prevents multiligand binding to CD11b but also blocks direct and indirect NHP T cell
alloresponses and prolongs survival of kidney allografts in NHP recipients. The main objective of this exploratory
R21 is to test the hypothesis that combining this mAb with anti-CD40 is safer and equivalent to or even more
effective than anti-CD154 in prolonging kidney xenograft survival in our established gene-edited pig-to-NHP
xenotransplantation model. A second objective of this study is to evaluate the effect of this combined blockade on
enumeration and function of T cell subsets in treated NHP. If successful, these studies may provide a basis for
prolonging kidney xenograft survival, thus addressing a pressing yet unmet medical need.

## Key facts

- **NIH application ID:** 10425736
- **Project number:** 1R21AI168393-01
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** M. AMIN ARNAOUT
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $242,440
- **Award type:** 1
- **Project period:** 2022-05-06 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10425736

## Citation

> US National Institutes of Health, RePORTER application 10425736, Effects of combining anti-CD40 and anti-CD11b mAb107 on survival of pig kidney xenografts in cynomolgus monkeys (1R21AI168393-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10425736. Licensed CC0.

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