Effect of Graft Perfusion With Two Cd45 Monoclonal Antibodies on Incidence of Kidney Allograft Rejection

Y, Brewer; Taube, David; Bewick, M.; Hale, Geoff; Dische, F. E.; Palmer, Arthur; Welsh, Ken I.; Bindon, C; Waldmann, Herman; Parsons, V.; Snowden, S.

doi:10.1016/s0140-6736(89)90951-3

Cited by 63 publications

(24 citation statements)

References 5 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In humans, perfusion of kidneys with anti-CD45 mAb before grafting has been reported to reduce the number of rejection episodes (27). More recently, it has been shown that the role of the direct vs indirect pathway of allorecognition depends on the type of tissue/organ graft, the experimental model, and the state of rejection (acute vs chronic) (28).…”

Section: Discussionmentioning

confidence: 99%

Heart, but Not Skin, Allografts from Donors Lacking Flt3 Ligand Exhibit Markedly Prolonged Survival Time

Wang¹,

Creus²,

Shufesky³

et al. 2004

The Journal of Immunology

View full text Add to dashboard Cite

Fms-like tyrosine kinase 3 ligand (Flt3L) administration leads to dramatic increases in dendritic cells (DC) in lymphoid and nonlymphoid tissues. Conversely, mice lacking Flt3L (Flt3L−/−) show severe reductions in both myeloid (CD11c+CD8α−) and lymphoid-related DC (CD11c+CD8α+) in the thymus and secondary lymphoid organs. In this study marked reductions in CD11c+ interstitial cardiac DC and in dermal, but not epidermal, DC (Langerhans cells) were also observed. CD11c+ cells that migrated from Flt3L−/− skin explants expressed lower surface MHC class II and costimulatory molecules and naive T cell allostimulatory activity than migratory wild-type (wt) C57BL/6 (B6) CD11c+ cells. We examined the survival of Flt3L−/− heart or tail skin grafts (H2b) in allogeneic wt (BALB/c; H2d) recipients. The outcome of transplantation of BALB/c organs into Flt3L−/− recipients was also determined. Flt3L−/− mice rejected BALB/c heart or skin grafts with similar kinetics as B6 wt recipients. Trafficking of donor DC into host spleens or draining lymph nodes was markedly reduced after transplantation of Flt3L−/− heart, but not skin grafts, respectively. Compared with wt hearts, survival of Flt3L−/− hearts was markedly prolonged in BALB/c recipients (median survival time, 37 and 15 days, respectively; p < 0.001). Skin graft survival was unaffected. Rejection of Flt3L−/− hearts was precipitated by infusion of wt donor DC at the time of transplant. Thus, severe depletion of interstitial heart DC resulting from targeted gene disruption prolongs, but does not indefinitely extend, heart survival. Acute rejection of wt grafts in Flt3L−/− recipients reflects presumably an intact role of the direct pathway of allorecognition.

show abstract

Section: Discussionmentioning

confidence: 99%

Heart, but Not Skin, Allografts from Donors Lacking Flt3 Ligand Exhibit Markedly Prolonged Survival Time

Wang¹,

Creus²,

Shufesky³

et al. 2004

The Journal of Immunology

View full text Add to dashboard Cite

show abstract

“…For our clinical studies, we used a pair of rat immunoglobulin G2 (IgG2) mAbs, which have a short half-life in humans, permitting rapid subsequent infusion of CTL. 18,19 To investigate if CD45 mAbs lymphodeplete NPC patients and allow for in vivo expansion of adoptively transferred EBV-specific CTL, we gave CD45 mAbs immediately before EBV-specific CTL infusion. Our results indicate that the approach is safe, results in transient lymphodepletion, and allows adoptively transferred CTL to expand even in NPC patients.…”

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

Enhancing the in vivo expansion of adoptively transferred EBV-specific CTL with lymphodepleting CD45 monoclonal antibodies in NPC patients

Louis

Straathof

Bollard

et al. 2009

Blood

107

View full text Add to dashboard Cite

Treatment of Epstein-Barr virus (EBV)-positive nasopharyngeal carcinoma (NPC) with EBV-specific cytotoxic T cells (EBV-specific IntroductionNasopharyngeal carcinoma (NPC) arises from the epithelial cells of the nasopharynx, and almost all nonkeratinizing and undifferentiated forms of this tumor are associated with Epstein-Barr virus (EBV). 1,2 NPC patients with limited local disease have a good prognosis when treated with chemotherapy and intensitymodulated radiation therapy, but outcomes in patients with locoregional bulky or metastatic disease remain poor. 1,3,4 In addition, patients who do survive frequently face severe short-and long-term treatment-related complications. 5,6 Hence, there is a need for novel therapies to improve disease-free survival and reduce treatmentrelated complications. Targeted T cell-based immunotherapy clearly has the potential to meet these needs. 7,8 Treatment of EBV-positive NPC with polyclonal EBV-specific cytotoxic T cells (EBV-specific CTL) has been promising, producing disease stabilization and complete remissions in patients with relapsed disease with low disease burden. [9][10][11] One of the primary obstacles in the treatment of NPC with EBV-specific CTL is the lack of expansion of the cells in the peripheral blood after infusion, so that the numbers of effector T cells available may be sufficient only for patients without bulky disease. This failure of CTL expansion in the periphery contrasts with the greater than 1000-fold expansion seen when EBV-specific CTL are given to patients during the period of lymphopenia after hematopoietic stem cell transplantation (HSCT) 12 or to patients with lymphoid malignancies, who have a relative lymphopenia. 13,14 Lymphoid depletion as a strategy to create space for the expansion of adoptively transferred cells has already shown evidence of success; melanoma patients receiving cyclophosphamide and fludarabine before the adoptive transfer of ex vivo expanded, melanomaspecific tumor-infiltrating lymphocytes (TILs), showed enhanced repopulation and proliferation of the transferred cells as well as regression of metastatic melanoma. 15,16 However, some of these patients remained profoundly immunocompromised and failed to regenerate an effective immune system. This poor immune reconstitution resulted in part from the extensive and nonspecific destruction of the resident immune system by the lymphodepleting cytotoxic drugs.Monoclonal antibodies (mAbs) that are cytolytic for lymphocytes may be an alternative means of producing lymphodepletion. The ideal antibody for T-cell depletion before CTL infusion should be effective but short lived in vivo, to permit rapid infusion and repopulation with infused CTL. We have used rat mAbs directed to the common leukocyte antigen CD45, which can deplete all leukocyte lineages. 17 This depletion was prolonged only in lymphoid lineages, as neutrophils began to recover 48 hours after injection. For our clinical studies, we used a pair of rat immunoglobulin G2 (IgG2) mAbs, which have a short half-life in humans...

show abstract

“…Early results [42] suggested that this approach may reduce the incidence of early graft rejection, and that its efficacy is related to percentage of cells binding anti-CD45 MoAb.…”

Section: Can Augmentation Of Donor Cell Chimaerism Promote Induction mentioning

confidence: 99%

Therapeutic advances in immunosuppression

Thomson

Forrester

1994

Clinical and Experimental Immunology

View full text Add to dashboard Cite

SUMMARYImmunosuppressive therapy is appropriate for the prevention or reversal of allograft rejection, and for the treatment of autoimmune disorders and allergic disease. Recent advances in our understanding of the cellular and molecular mechanisms that regulate immune responses have paralleled elucidation of the modes of action of a variety of therapeutic immunosuppressive agents, both 'old' and new. These developments have identified potential targets for more refined and specific intervention strategies that are now being tested in the clinic.

show abstract

Effect of Graft Perfusion With Two Cd45 Monoclonal Antibodies on Incidence of Kidney Allograft Rejection

Cited by 63 publications

References 5 publications

Heart, but Not Skin, Allografts from Donors Lacking Flt3 Ligand Exhibit Markedly Prolonged Survival Time

Heart, but Not Skin, Allografts from Donors Lacking Flt3 Ligand Exhibit Markedly Prolonged Survival Time

Enhancing the in vivo expansion of adoptively transferred EBV-specific CTL with lymphodepleting CD45 monoclonal antibodies in NPC patients

Therapeutic advances in immunosuppression

Contact Info

Product

Resources

About