Stem cell comparison: what can we learn clinically from unrelated cord blood transplantation as an alternative stem cell source?

Milano, Filippo; Boelens, Jaap Jan

doi:10.1016/j.jcyt.2015.03.003

Cited by 4 publications

(5 citation statements)

References 57 publications

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“…Nowadays, some centers regard CB to be the preferred cell source for patients at high risk of relapse with or without minimal residual disease pretransplant. [19] This is supported by the lower probability of relapse in majority of studies, even in very high-risk, MRD-positive patients. [2,17] The less stringent HLA-matching resulting in more HLA-disparity [20] may explain this lower probability of relapse observed in CBT when compared to MUD and MMUD.…”

Section: Umbilical Cbtmentioning

confidence: 82%

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Individualized conditioning regimes in cord blood transplantation: Towards improved and predictable safety and efficacy

Admiraal

Boelens

2016

Expert Opinion on Biological Therapy

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Individualization of agents used in the conditioning regimen in CBT has proven its added value. Further fine-tuning, including new drugs and/or comprehensive models for all drugs, may result in better predictable conditioning regimens. A predictable conditioning regimen is also of interest/importance when studying adjuvant therapies, including immunotherapies (e.g. cellular vaccines or engineered T-cell) in a harmonized clinical trial design setting.

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Section: Umbilical Cbtmentioning

confidence: 82%

“…[36] Additionally, CB-derived T cells mediate a more powerful antileukemic effect [13] and tumor responses compared to adult T cells. [2,6,19] A drawback of this strategy may be an increased incidence of GvHD. This was described in other manuscript from same group, but this GvHD was mainly acute and not chronic and did not influence TRM.…”

Section: T-cell Irmentioning

confidence: 99%

Individualized conditioning regimes in cord blood transplantation: Towards improved and predictable safety and efficacy

Admiraal

Boelens

2016

Expert Opinion on Biological Therapy

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“…Although the reasons for this are incompletely understood, several factors, such as the intensity of the immunosuppression in haplo-identical AHCT, or the intrinsic features of the graft in terms of cell composition and functionality in cord blood transplants, may contribute to this observation (29,30). Moreover, in certain circumstances, the risk of relapse appears to be lower following these mismatched transplants, arguing in favor of enhanced GVT in these settings (31)(32)(33). Based on the presumption that anti-HLA T-cell reactivity is an effective antineoplastic mechanism, the infusion of intentionally mismatched peripheral blood mononuclear cells following chemotherapy is being investigated as a form of immunological consolidation after chemotherapy (34).…”

Section: Target Antigens In Hematological Cancers Histocompatibility mentioning

confidence: 99%

T-Cell Immunotherapies Targeting Histocompatibility and Tumor Antigens in Hematological Malignancies

et al. 2020

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Over the last decades, T-cell immunotherapy has revealed itself as a powerful, and often curative, strategy to treat blood cancers. In hematopoietic cell transplantation, most of the so-called graft-vs.-leukemia (GVL) effect hinges on the recognition of histocompatibility antigens that reflect immunologically relevant genetic variants between donors and recipients. Whether other variants acquired during the neoplastic transformation, or the aberrant expression of gene products can yield antigenic targets of similar relevance as the minor histocompatibility antigens is actively being pursued. Modern genomics and proteomics have enabled the high throughput identification of candidate antigens for immunotherapy in both autologous and allogeneic settings. As such, these major histocompatibility complex-associated tumor-specific (TSA) and tumor-associated antigens (TAA) can allow for the targeting of multiple blood neoplasms, which is a limitation for other immunotherapeutic approaches, such as chimeric antigen receptor (CAR)-modified T cells. We review the current strategies taken to translate these discoveries into T-cell therapies and propose how these could be introduced in clinical practice. Specifically, we discuss the criteria that are used to select the antigens with the greatest therapeutic value and we review the various T-cell manufacturing approaches in place to either expand antigen-specific T cells from the native repertoire or genetically engineer T cells with minor histocompatibility antigen or TSA/TAA-specific recombinant T-cell receptors. Finally, we elaborate on the current and future incorporation of these therapeutic T-cell products into the treatment of hematological malignancies.

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“…One of the main advantages of CB is the fact that an increased level of HLA disparity can be tolerated (166). The current standard for CB selection is donor–recipient matching at six HLA loci, namely, HLA-A, HLA-B antigen, and HLA-DRB1 allele in comparison to 8–10 loci for BM or PBSC donation (167, 168).…”

Section: Stem Cell Sourcesmentioning

confidence: 99%

Milestones of Hematopoietic Stem Cell Transplantation – From First Human Studies to Current Developments

et al. 2016

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Since the early beginnings, in the 1950s, hematopoietic stem cell transplantation (HSCT) has become an established curative treatment for an increasing number of patients with life-threatening hematological, oncological, hereditary, and immunological diseases. This has become possible due to worldwide efforts of preclinical and clinical research focusing on issues of transplant immunology, reduction of transplant-associated morbidity, and mortality and efficient malignant disease eradication. The latter has been accomplished by potent graft-versus-leukemia (GvL) effector cells contained in the stem cell graft. Exciting insights into the genetics of the human leukocyte antigen (HLA) system allowed improved donor selection, including HLA-identical related and unrelated donors. Besides bone marrow, other stem cell sources like granulocyte-colony stimulating-mobilized peripheral blood stem cells and cord blood stem cells have been established in clinical routine. Use of reduced-intensity or non-myeloablative conditioning regimens has been associated with a marked reduction of non-hematological toxicities and eventually, non-relapse mortality allowing older patients and individuals with comorbidities to undergo allogeneic HSCT and to benefit from GvL or antitumor effects. Whereas in the early years, malignant disease eradication by high-dose chemotherapy or radiotherapy was the ultimate goal; nowadays, allogeneic HSCT has been recognized as cellular immunotherapy relying prominently on immune mechanisms and to a lesser extent on non-specific direct cellular toxicity. This chapter will summarize the key milestones of HSCT and introduce current developments.

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Stem cell comparison: what can we learn clinically from unrelated cord blood transplantation as an alternative stem cell source?

Cited by 4 publications

References 57 publications

Individualized conditioning regimes in cord blood transplantation: Towards improved and predictable safety and efficacy

Individualized conditioning regimes in cord blood transplantation: Towards improved and predictable safety and efficacy

T-Cell Immunotherapies Targeting Histocompatibility and Tumor Antigens in Hematological Malignancies

Milestones of Hematopoietic Stem Cell Transplantation – From First Human Studies to Current Developments

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