De Novo Malignancies After Transplantation

Doycheva, I.B.; Amer, Syed; Watt, Kymberly D.

doi:10.1016/j.mcna.2016.01.006

Cited by 52 publications

(39 citation statements)

References 115 publications

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“…[8,9] A preferable approach would be to dampen aberrant immune responses towards self-antigens, while maintaining the full capacity of the immune system to mount responses against foreign antigens and pathogens. A number of clinical trials have attempted to treat patients with autoimmune diseases in an antigen-specific manner by delivering disease-associated proteins either orally or nasally to target tolerogenic mucosal DCs.…”

Section: Introductionmentioning

confidence: 99%

Multicomponent Injectable Hydrogels for Antigen‐Specific Tolerogenic Immune Modulation

Verbeke

Gordo

Schubert

et al. 2017

Adv Healthcare Materials

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Biomaterial scaffolds that enrich and modulate immune cells in situ can form the basis for potent immunotherapies to elicit immunity or reëstablish tolerance. Here, we explore the potential of an injectable, porous hydrogel to induce a regulatory T cell (Treg) response by delivering a peptide antigen to dendritic cells (DCs) in a non-inflammatory context. Two methods are described for delivering the BDC peptide from pore-forming gels in the NOD (non-obese diabetic) mouse model of type 1 diabetes: encapsulation in poly(lactide-co-glycolide) (PLG) microparticles, or direct conjugation to the alginate polymer. While particle-based delivery leads to antigen-specific T cells responses in vivo, PLG particles alter the phenotype of the cells infiltrating the gels. Following gel-based peptide delivery, transient expansion of endogenous antigen-specific T cells is observed in the draining lymph nodes. Antigen-specific T cells accumulate in the gels, and, strikingly, ~60% of the antigen-specific CD4+ T cells in the gels are Tregs. Antigen-specific T cells are also enriched in the pancreatic islets, and administration of peptide-loaded gels does not accelerate diabetes. This work demonstrates that a non-inflammatory biomaterial system can generate antigen-specific Tregs in vivo, which may enable the development of new therapies for the treatment of transplant rejection or autoimmune diseases.

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Section: Introductionmentioning

confidence: 99%

Multicomponent Injectable Hydrogels for Antigen‐Specific Tolerogenic Immune Modulation

Verbeke

Gordo

Schubert

et al. 2017

Adv Healthcare Materials

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“…30,31 After SOT, PTLD is one of the most common malignancy, following nonmelanoma skin cancer. [32][33][34] The cumulative incidence after 5 years ranges from 1% to 10%, with highest rates up to 33% in small bowel and multivisceral transplantation (Table 2). 35,36 Major risk factors for developing PTLD …”

Section: Pathogenesis and Classificationmentioning

confidence: 99%

Risk factors, diagnosis, and management of posttransplant lymphoproliferative disorder: improving patient outcomes with a multidisciplinary treatment approach

Ligeti¹,

Müller²,

Müller‐Tidow³

et al. 2017

TRRM

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“…Nevertheless, the acute and chronic morbidity from the end‐organ side effects of life‐long systemic immunosuppression (IS), for example with calcineurin inhibitors, including but not limited to diabetes, chronic kidney disease, or neoplasia, has curtailed wider adoption of VCA. Novel immunomodulatory or donor‐specific graft tolerance strategies that obviate the need for toxic conditioning or long‐term IS are thus an imminent need in expanding the indications for VCA …”

Section: Introductionmentioning

confidence: 99%

Adipose-derived stromal cell therapy combined with a short course nonmyeloablative conditioning promotes long-term graft tolerance in vascularized composite allotransplantation

Schweizer

Taddeo

Waldner

et al. 2020

American Journal of Transplantation

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The risks of chronic immunosuppression limit the utility of vascularized composite allotransplantation (VCA) as a reconstructive option in complex tissue defects. We evaluated a novel, clinically translatable, radiation-free conditioning protocol that combines anti-lymphocyte serum (ALS), tacrolimus, and cytotoxic T-lymphocyteassociated protein 4 immunoglobulin (CTLA4-Ig) with adipose-derived stromal cells (ASCs) to allow VCA survival without long-term systemic immunosuppression. Fullmismatched rat hind-limb-transplant recipients received tacrolimus (0.5 mg/kg) for 14 days and were assigned to 4 groups: controls (CTRL) received no conditioning;ASC-group received CTLA4-Ig (10 mg/kg body weight i.p. postoperative day [POD] 2, 4, 7) and donor ASCs (1 × 10 6 iv, POD 2, 4, 7, 15, 28); the ASC-cyclophosphamide (CYP)-group received CTLA4-Ig, ASC plus cyclophosphamide (50 mg/kg ip, POD 3); the ASC-ALS-group received CTLA4-Ig, ASCs plus ALS (500 µL ip, POD 1, 5). Banff grade III or 120 days were endpoints. ASCs suppressed alloresponse in vitro. Median rejection-free VCA survival was 28 days in CTRL (n = 7), 34 in ASC (n = 6), and 27.5 in ASC-CYP (n = 4). In contrast, ASC-ALS achieved significantly longer, rejection-free VCA survival in 6/7 animals (86%), with persistent mixed donor-cell chimerism, and elevated systemic and allograft skin T regs , with no signs of acute cellular rejection.Taken together, a regimen comprised of short-course tacrolimus, repeated CTLA4-Ig and ASC administration, combined with ALS, promotes long-term VCA survival without chronic immunosuppression. K E Y W O R D S basic (laboratory) research/science, cellular transplantation (nonislet), cytokines/cytokine receptors, immunosuppressant -fusion proteins and monoclonal antibodies: belatacept, immunosuppression/immune modulation, immunosuppressive regimens, stem cells, tolerance: costimulation blockade, translational research/science, vascularized composite and reconstructive transplantation | 1273 SCHWEIZER Et al. S U PP O RTI N G I N FO R M ATI O N Additional supporting information may be found online in the Supporting Information section. How to cite this article: Schweizer R, Taddeo A, Waldner M, et al. Adipose-derived stromal cell therapy combined with a short course nonmyeloablative conditioning promotes long-term graft tolerance in vascularized composite allotransplantation. Am J Transplant. 2020;20:1272-1284.

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De Novo Malignancies After Transplantation

Cited by 52 publications

References 115 publications

Multicomponent Injectable Hydrogels for Antigen‐Specific Tolerogenic Immune Modulation

Multicomponent Injectable Hydrogels for Antigen‐Specific Tolerogenic Immune Modulation

Risk factors, diagnosis, and management of posttransplant lymphoproliferative disorder: improving patient outcomes with a multidisciplinary treatment approach

Adipose-derived stromal cell therapy combined with a short course nonmyeloablative conditioning promotes long-term graft tolerance in vascularized composite allotransplantation

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