Costimulatory Blockade and Solid Organ Transplantation: The Past, Present, and Future

Kitchens, William H.; Larsen, Christian P.; Badell, I. Raul

doi:10.1016/j.ekir.2023.08.037

Cited by 6 publications

(4 citation statements)

References 129 publications

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“…Belatacept, a unique FDA-approved co-stimulation inhibitor, offers a novel approach to immunosuppression in solid organ transplantation, particularly in kidney transplantation. Unlike traditional immunosuppressants that target T cells directly, belatacept inhibits T cell activation by blocking co-stimulatory signals necessary for their activation [ 41 , 125 ].…”

Section: Discussionmentioning

confidence: 99%

“…Belatacept (LEA29Y) represents an alternative to abatacept, the difference being its higher affinity for target receptors and higher potency [ 41 , 66 , 67 ].…”

Section: Immunologic Strategies In Vcamentioning

confidence: 99%

“…Table 1. A review of the costimulatory molecules classification according to their structure, in four major groups (families): [34][35][36][38][39][40][41][42][43][44][45][46][47][48][49]. CD28 represents the main costimulatory receptor of the B7 family.…”

Section: Targeting Costimulatory Pathways In Transplant Patientsmentioning

confidence: 99%

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Exploring Costimulatory Blockade-Based Immunologic Strategies in Transplantation: Are They a Promising Immunomodulatory Approach for Organ and Vascularized Composite Allotransplantation?

Grosu-Bularda,

Hodea,

Zamfirescu

et al. 2024

JPM

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The field of transplantation, including the specialized area of vascularized composite allotransplantation (VCA), has been transformed since the first hand transplant in 1998. The major challenge in VCA comes from the need for life-long immunosuppressive therapy due to its non-vital nature and a high rate of systemic complications. Ongoing research is focused on immunosuppressive therapeutic strategies to avoid toxicity and promote donor-specific tolerance. This includes studying the balance between tolerance and effector mechanisms in immune modulation, particularly the role of costimulatory signals in T lymphocyte activation. Costimulatory signals during T cell activation can have either stimulatory or inhibitory effects. Interfering with T cell activation through costimulation blockade strategies shows potential in avoiding rejection and prolonging the survival of transplanted organs. This review paper aims to summarize current data on the immunologic role of costimulatory blockade in the field of transplantation. It focuses on strategies that can be applied in vascularized composite allotransplantation, offering insights into novel methods for enhancing the success and safety of these procedures.

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Section: Discussionmentioning

confidence: 99%

“…Belatacept (LEA29Y) represents an alternative to abatacept, the difference being its higher affinity for target receptors and higher potency [ 41 , 66 , 67 ].…”

Section: Immunologic Strategies In Vcamentioning

confidence: 99%

See 1 more Smart Citation

Exploring Costimulatory Blockade-Based Immunologic Strategies in Transplantation: Are They a Promising Immunomodulatory Approach for Organ and Vascularized Composite Allotransplantation?

Grosu-Bularda,

Hodea,

Zamfirescu

et al. 2024

JPM

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“…Belatacept was initially approved for organ rejection prophylaxis in kidney recipients and has become an essential alternative to calcineurin inhibitors (CNIs), given its lower risk of nephrotoxicity, decreased pill burden, and lack of therapeutic monitoring [ 3 , 4 ]. Other organ programs are now adopting belatacept for similar reasons, in addition to its benefits in recipients who are highly sensitized [ 5–7 ].…”

mentioning

confidence: 99%

An Unexpectedly High Incidence of Invasive Fungal Diseases in Solid Organ Transplant Recipients Taking Belatacept for Organ Rejection Prophylaxis: A Single-Center Retrospective Cohort Study

Bell,

Pisano,

Brown

et al. 2024

Open Forum Infectious Diseases

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Characterizing coagulation responses in humans and nonhuman primates following kidney xenotransplantation—A narrative review

Zidan,

El‐Sherbini,

Noureldin

et al. 2024

American J Hematol

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The recent report of the first pig kidney transplant in a living human brings hope to thousands of people with end‐stage kidney failure. The scientific community views this early success with caution as kidney xenotransplantation exhibits many challenges and barriers. One of these is coagulation dysregulation. This includes (i) pig von Willebrand Factor (vWF) interaction with human platelets, which can induce abnormal clotting responses, heightening the risk of graft failure, (ii) the inefficiency of pig thrombomodulin in activating human protein C, which emphasizes the species‐specific variations that aggravate coagulation challenges, and (iii) the development of thrombotic microangiopathy in the pig grafts and the occurrence of systemic consumptive coagulopathy in the recipients. Indeed, coagulation dysregulation largely results from differences in endothelial cell response and incompatibilities between pig and human coagulation–anticoagulation pathways. These barriers can be resolved by modifications to pig vWF and the expression of human thrombomodulin and endothelial protein C receptors in pig cells, serving as strategic interventions to align the coagulation systems of the two species more closely. These coagulation challenges have clinical implications in how they affect graft survival and patient outcome. Genetic engineering of the organ‐source pig and the administration of various drugs have assisted in correcting this coagulation dysregulation. Hence, comprehending and controlling coagulation dysregulation is crucial for progress in xenotransplantation as a viable option for treating patients with terminal kidney disease.

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Costimulatory Blockade and Solid Organ Transplantation: The Past, Present, and Future

Cited by 6 publications

References 129 publications

Exploring Costimulatory Blockade-Based Immunologic Strategies in Transplantation: Are They a Promising Immunomodulatory Approach for Organ and Vascularized Composite Allotransplantation?

Exploring Costimulatory Blockade-Based Immunologic Strategies in Transplantation: Are They a Promising Immunomodulatory Approach for Organ and Vascularized Composite Allotransplantation?

An Unexpectedly High Incidence of Invasive Fungal Diseases in Solid Organ Transplant Recipients Taking Belatacept for Organ Rejection Prophylaxis: A Single-Center Retrospective Cohort Study

Characterizing coagulation responses in humans and nonhuman primates following kidney xenotransplantation—A narrative review

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