Prolonged Survival of Pig Orthotopic Heart Grafts Treated With Cyclosporin A

Calne, R. Y.; White, David J.; Rolles, K; Smith, D. P.; Herbertson, B. M.

doi:10.1016/s0140-6736(78)90971-6

Cited by 186 publications

(52 citation statements)

References 7 publications

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“…Other data indicate that CsA, as a single agent, can induce immunologic tolerance to a solid organ allograft [31][32][33] and be B6 mice were irradiated with 200 cGy TBI on day Ϫ 1 and infused with 40 ϫ 10 6 BALB/c BM on day 0. Reagents were administered from day Ϫ 1 through day ϩ 6.…”

Section: Discussionmentioning

confidence: 99%

Combined effects of calcineurin inhibitors or sirolimus with anti-CD40L mAb on alloengraftment under nonmyeloablative conditions

Taylor

Lees

Wilson

et al. 2002

Blood

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The immunosuppressive drugs, cyclosporine A (CsA), tacrolimus, or sirolimus, were analyzed as single agents and in combination with anti-CD40L monoclonal antibody (mAb) for their effects on alloengraftment in mice conditioned with minimal total body irradiation (TBI). Whereas anti-CD40L mAb facilitated chimerism, neither sirolimus nor CsA resulted in substantial alloengraftment. However, sirolimus was synergistic with anti-CD40L mAb for inducing donor chimerism. Contrary to expectations, CsA, a T-cell receptor (TCR) signaling inhibitor, did not abrogate anti-CD40L mAb-facilitated engraftment but rather increased engraftment in anti-CD40L mAb-treated mice. Although tacrolimus alone or with anti-CD40L mAb resulted in similar levels of donor chimerism, donor T-cell reconstitution was very low in tacrolimus-treated mice. At 1 week after transplantation, CsA decreased thymic numbers more profoundly than sirolimus or tacrolimus in anti-CD40L mAbtreated recipients. In contrast, only sirolimus resulted in a decrease in host splenic T-cell numbers in anti-CD40L mAbtreated recipients. Importantly, sirolimus and anti-CD40L mAb induced profound donor tolerance with 100% acceptance of donor skin grafts placed early after bone marrow transplantation (BMT). In contrast, anti-CD40L mAb alone or in combination with CsA resulted in 12% or less donor skin graft acceptance early (1 month) and 60% or less later (3 months) after BMT. These data have clinical relevance and indicate that immunosuppressive pharmacologic agents enhance anti-CD40L mAb-facilitated alloengraftment and tolerance induction under nonmyeloablative conditioning. (Blood. 2002; 100:3400-3407)

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Section: Discussionmentioning

confidence: 99%

Combined effects of calcineurin inhibitors or sirolimus with anti-CD40L mAb on alloengraftment under nonmyeloablative conditions

Taylor

Lees

Wilson

et al. 2002

Blood

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“…The method to measure cyclosporine blood levels was developed at the same time (17). After Borel's lecture at the British Society for Immunology in London in April 1976, multiple investigators tested cyclosporine in transplant animal models-heart transplant in rat and pig models and kidney transplant in rabbit and dog models (4,(18)(19)(20)-with excellent results. These encouraging results in animal studies were translated into human trials around the same time.…”

Section: Preclinical and Clinical Studiesmentioning

confidence: 99%

Calcineurin Inhibitors: 40 Years Later, Can’t Live Without …

Azzi

Sayegh

Mallat

2013

The Journal of Immunology

285

210

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Calcineurin inhibitors (CNIs) revolutionized the field of organ transplantation and remain the standard of care 40 years after the discovery of cyclosporine. The early impressive results of cyclosporine in kidney transplant recipients led to its subsequent use in other organ transplant recipients and for treatment of a variety of autoimmune diseases as well. In this review, we examine the discovery of CNIs, their mechanism of action, preclinical and clinical studies with CNIs, and the usage of CNIs in nontransplant recipients. We review the mechanisms of renal toxicity associated with CNIs and the recent efforts to avoid or reduce usage of these drugs. Although minimization strategies are possible, safe, and of potential long-term benefit, complete avoidance of CNIs has proven to be more challenging than initially thought.

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“…Inspired by the presentation, White acquired some CyA and conducted repeated experiments at Calne's laboratory. They demonstrated that CyA prolonged allograft survival of heart transplants in rats [28], renal transplants in dogs [29], and heart transplants in pigs (15 or 25 mg/kg of CyA intramuscularly) [30].…”

Section: Dawn Of a New Era: The Arrival Of "Cyclosporine"mentioning

confidence: 99%

The Contribution of Pharmacological Agents in the History of Organ Transplantation

Kawakami¹

2013

Pharm Anal Acta

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Prolonged Survival of Pig Orthotopic Heart Grafts Treated With Cyclosporin A

Cited by 186 publications

References 7 publications

Combined effects of calcineurin inhibitors or sirolimus with anti-CD40L mAb on alloengraftment under nonmyeloablative conditions

Combined effects of calcineurin inhibitors or sirolimus with anti-CD40L mAb on alloengraftment under nonmyeloablative conditions

Calcineurin Inhibitors: 40 Years Later, Can’t Live Without …

The Contribution of Pharmacological Agents in the History of Organ Transplantation

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