High-throughput minor histocompatibility antigen prediction

DeLuca, David S.; Ladas, Nektarios; Khattab, Barbara; Blasczyk, Rainer

doi:10.1093/bioinformatics/btp404

Cited by 12 publications

(10 citation statements)

References 30 publications

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“…Because of the HLA specificity of mHA presentation and the heterogeneity in HLA across various populations, a picture of considerable heterogeneity in outcomes has emerged in URD transplant recipients. 30,32 This heterogeneity also affects the risk of GVHD observed in URD-recipient pairs matched for HLA, though this risk is lower than that recorded with one or more HLA mismatches. 33,34 Whereas recipients of stringently matched URD SCT have been reported to have outcomes similar to MRD allografts in specific populations, 35 other studies evaluating disparity at the MHC locus have shown that mismatching for loci such as HLA-DPB1 increases the odds for developing GVHD or reducing relapse, as does receiving a SCT from an MHC haplotype mismatched URD who is otherwise matched at allele level for the HLA-A, B, C and DRB1 loci.…”

Section: Discussionmentioning

confidence: 99%

Anti-thymocyte globulin for conditioning in matched unrelated donor hematopoietic cell transplantation provides comparable outcomes to matched related donor recipients

Portier

Sabo

Roberts

et al. 2012

Bone Marrow Transplant

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Rabbit anti-thymocyte globulin (ATG) is used as prophylaxis against GVHD following allogeneic hematopoietic cell transplantation (HCT). At our institution, ATG is exclusively used in the conditioning of matched unrelated donor (URD) transplant recipients. A total of 50 URD HCT recipients who received ATG (ATG group) were retrospectively compared with 48 matched related donor (MRD) HCT recipients who did not receive ATG (no ATG group). There were no significant differences between the groups in rates of day 100 mortality, acute GVHD or relapse. Chronic GVHD incidence was significantly lower in the ATG group (P = 0.007). At a median follow-up of 36 months in the entire cohort, 50% patients are alive in the ATG group and 63% of the patients are alive in the no ATG group (P = 0.13). We conclude that the administration of ATG to patients undergoing URD HCT preserves the anti-leukemia benefit of the transplant, while reducing the risk of developing GVHD, resulting in OS rates that are comparable to MRD HCT recipients.

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Section: Discussionmentioning

confidence: 99%

Anti-thymocyte globulin for conditioning in matched unrelated donor hematopoietic cell transplantation provides comparable outcomes to matched related donor recipients

Portier

Sabo

Roberts

et al. 2012

Bone Marrow Transplant

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“…However, the success of donor vaccination will depend on the availability of a sufficient number of miHAs with allele frequencies such that an appropriate miHA is available for a meaningful fraction of donor/recipient pairs. New biocomputational approaches for identifying miHAs have accelerated the pace of miHA identification, 34,49,50 making it reasonable to propose that appropriate candidate miHAs will be identified for many patients in the near future.…”

Section: Memory T Cells From Miha-vaccinated Donors Improve Gvl 5973mentioning

confidence: 99%

Memory T cells from minor histocompatibility antigen–vaccinated and virus-immune donors improve GVL and immune reconstitution

Matte-Martone²,

Zheng³

et al. 2011

Blood

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IntroductionAllogeneic hematopoietic stem cell transplantation (alloSCT) can be a curative therapy for patients with hematologic malignancies. Mature donor T cells in the allograft are critical for reconstituting T-cell immunity in recipients and mediate an alloimmune antileukemia/lymphoma effect called GVL. In MHC-matched alloSCT, alloimmune T cells target minor histocompatibility antigens (miHAs), which are peptide products of polymorphic genes that distinguish hosts from donors. 1 Unfortunately, alloreactive T cells also attack normal host tissues, causing GVHD. A longstanding and elusive goal in the alloSCT field has been to develop approaches that preserve GVL and immune reconstitution while minimizing GVHD. A second challenge has been how to augment GVL to overcome GVL resistance, as cancer relapse is the single greatest cause of death after transplantation. 2 The risk of relapse is not spread evenly across cancer types. Some malignancies, such as chronic-phase chronic myelogenous leukemia (CP-CML), are extremely GVL sensitive, 3 whereas other types of leukemias, such as blast-crisis CML (BC-CML) and acute myelogenous leukemia, are relatively GVL-resistant. 3,4 One approach for improving GVL would be to broadly augment the alloimmune response by reducing the intensity of immunosuppression. However, this increases the risk for serious and lifethreatening GVHD. 5 Another strategy has been to develop T-cell therapies with a single target specificity, such as those that recognize a single miHA, with the idea that such T cells could augment GVL with a reduced risk for inducing GVHD. 1,6 These T cells can be clonal, polyclonal, or genetically modified to express defined antigen receptors. 7,8 Although there are some promising results, 9,10 such approaches have not yet been widely applied. Transferred cells have in general not survived well in vivo, perhaps because they were activated effectors. In addition, these methodologies are labor intensive and require technical expertise and facilities not available at most centers.We reasoned that an alternative to T-cell engineering would be to increase the frequency of allograft T cells that mediate GVL by vaccinating donors against a single miHA. There is evidence that functional T-cell memory against miHAs can be generated in vivo in humans. [11][12][13] GVHD is increased when donors are multiparous, 12 presumably because of priming against fetal miHAs. Blood transfusion of even aplastic anemia patients increases the risk of HLA-matched allograft rejection. 13 If donors could be vaccinated against single miHAs, then the selective transfer of donor memory T cells (T M ) could improve GVL. T M generated in the donor by prior pathogen infection would also be transferred, thereby augmenting immune reconstitution.In the present study, we show that miHA vaccination of donors greatly increases CD8 ϩ T M -mediated GVL against GVL-sensitive mouse CP-CML (mCP-CML) 14 and GVL-resistant mouse BC-CML (mBC-CML) 15 induced by bcr-abl or bcr-abl and NUP98/ HOXA9 fusion cDNAs, respec...

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“…Alternatively, reverse immunology approaches may help in identifying clinically relevant minor H antigens. Datasets, software, and computational power seem to be sufficient to generate candidate minor H antigens . Although three autosomally encoded minor H antigens have been identified by the reverse immunology , the major bottleneck seems to be cellular confirmation of the predicted epitopes.…”

Section: Minor H Antigen Identificationmentioning

confidence: 99%

Minor histocompatibility antigens: past, present, and future

Spierings

2014

Tissue Antigens

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Minor histocompatibility (H) antigens are key molecules driving allo-immune responses in both graft-versus-host-disease (GvHD) and in graft-versus-leukemia (GvL) reactivity in human leukocyte antigen (HLA)-matched hematopoietic stem-cell transplantation (HSCT). Dissection of the dual function of minor H antigens became evident through their different modes of tissue and cell expression, i.e. hematopoietic system-restricted or broad. Broadly expressed minor H antigens can cause both GvHD and GvL effects, while hematopoietic system-restricted minor H antigens are more prone to induce GvL responses. This phenomenon renders the latter group of minor H antigens as curative tools for HSCT-based immunotherapy of hematological malignancies and disorders, in which minor H antigen-specific responses are enhanced in order to eradicate the malignant cells. This article describes the immunogenetics of minor H antigens and methods that have been developed to identify them. Moreover, it summarizes the clinical relevance of minor H antigens in transplantation, with special regards to allogeneic HSCT and solid-organ transplantation.

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High-throughput minor histocompatibility antigen prediction

Abstract: http://www.peptidecheck.org.

Cited by 12 publications

References 30 publications

Anti-thymocyte globulin for conditioning in matched unrelated donor hematopoietic cell transplantation provides comparable outcomes to matched related donor recipients

Anti-thymocyte globulin for conditioning in matched unrelated donor hematopoietic cell transplantation provides comparable outcomes to matched related donor recipients

Memory T cells from minor histocompatibility antigen–vaccinated and virus-immune donors improve GVL and immune reconstitution

Minor histocompatibility antigens: past, present, and future

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