The DOI matches its Crossref record; 18 of the 18 references it cites were found in a registry or an index.
CTLA4-Ig and anti-CD40 ligand prevent renal allograft rejection in primates
Open accessAbstract
Selective inhibition of T cell costimulation using the B7-specific fusion protein CTLA4-Ig has been shown to induce long-term allograft survival in rodents. Antibodies preventing the interaction between CD40 and its T cell-based ligand CD154 (CD40L) have been shown in rodents to act synergistically with CTLA4-Ig. It has thus been hypothesized that these agents might be capable of inducing long-term acceptance of allografted tissues in primates. To test this hypothesis in a relevant preclinical model, CTLA4-Ig and the CD40L-specific monoclonal antibody 5C8 were tested in rhesus monkeys. Both agents effectively inhibited rhesus mixed lymphocyte reactions, but the combination was 100 times more effective than either drug alone. Renal allografts were transplanted into nephectomized rhesus monkeys shown to be disparate at major histocompatibility complex class I and class II loci. Control animals rejected in 5–8 days. Brief induction doses of CTLA4-Ig or 5C8 alone significantly prolonged rejection-free survival (20–98 days). Two of four animals treated with both agents experienced extended (>150 days) rejection-free allograft survival. Two animals treated with 5C8 alone and one animal treated with both 5C8 and CTLA4-Ig experienced late, biopsy-proven rejection, but a repeat course of their induction regimen successfully restored normal graft function. Neither drug affected peripheral T cell or B cell counts. There were no clinically evident side effects or rejections during treatment. We conclude that CTLA4-Ig and 5C8 can both prevent and reverse acute allograft rejection, significantly prolonging the survival of major histocompatibility complex-mismatched renal allografts in primates without the need for chronic immunosuppression.
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Cites
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Cited by
The Danger Model: A Renewed Sense of Self
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Recent advances in (therapeutic protein) drug development
Lagassé, H. A. D., Alexaki, A., Simhadri, V. L., Katagiri, N. H., Jankowski, W., Sauna, Z. E., & Kimchi-Sarfaty, C. (2017) · F1000Research · doi:10.12688/f1000research.9970.1 · Cited by 481
Transplantation of Anergic Histoincompatible Bone Marrow Allografts
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Metadata
- Authors
- Kirk, A. D., Harlan, D. M., Armstrong, N. N., Davis, T. A., Dong, Y., Gray, G. S., Hong, X., Thomas, D., Fechner, J. H., & Knechtle, S. J.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 1997-08-05
- Volume
- 94
- Issue
- 16
- Pages
- 8789-8794
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2118061894
- Cited by
- 929
- References
- 18
- FWCI
- 42.40
- Type
- journal article
- Language
- en
- Open access
- green
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- CoChat. (2026). Citation check: CTLA4-Ig and anti-CD40 ligand prevent renal allograft rejection in primates. https://app.cochat.ai/papers/10.1073/pnas.94.16.8789
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- Kirk, A. D., Harlan, D. M., Armstrong, N. N., Davis, T. A., Dong, Y., Gray, G. S., Hong, X., Thomas, D., Fechner, J. H., & Knechtle, S. J. (1997). CTLA4-Ig and anti-CD40 ligand prevent renal allograft rejection in primates. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.94.16.8789
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
