Dendritic cell vaccination in an allogeneic stem cell recipient receiving a transplant from a human cytomegalovirus (HCMV)-seronegative donor: induction of a HCMV-specific Thelper cell response

Feuchtinger, Tobias; Opherk, Kathrin; Bicanic, Oliver; Schumm, Michael; Grigoleit, Götz Ulrich; Hamprecht, Klaus; Jahn, Gerhard; Handgretinger, Rupert; Lang, Peter

doi:10.3109/14653241003587645

Cited by 14 publications

(13 citation statements)

References 19 publications

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“…Therefore, repopulating capacity and hence the Tcell phenotype have a strong influence on the success of T-cell transfer. 39,40 The GMP-protocol presented here, shows a strong potential of proliferation of both CD4…”

Section: Discussionmentioning

confidence: 88%

Rapid generation of NY-ESO-1-specific CD4⁺T_HELPER1 cells for adoptive T-cell therapy

et al. 2015

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Section: Discussionmentioning

confidence: 88%

Rapid generation of NY-ESO-1-specific CD4⁺T_HELPER1 cells for adoptive T-cell therapy

et al. 2015

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“…Although vaccine-induced immunity is becoming advisable in a number of clinical conditions (41)(42)(43) whether alloreactive T cell responses, frequently observed in the context of allotransplantation, might interfere with vaccine immunogenicity remained to be determined. Although our previous study provided the proof of principle that minor H antigen-and tumor-specific T cells could team up for prostate cancer rejection and highlighted the importance of posttransplant tumorspecific vaccination (26), it focused on alloresponse to Y-encoded H Ags and did not determine whether vaccine-immunogenicity could be influenced (either promoted or impinged) by concomitant alloreactivity.…”

Section: Discussionmentioning

confidence: 99%

Concurrent Allorecognition Has a Limited Impact on Posttransplant Vaccination

Manzo

Michelini

Basso

et al. 2011

The Journal of Immunology

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Transplantation of allogeneic hematopoietic stem cells with or without immunocompetent lymphocytes has proved a successful strategy in the treatment of hematological malignancies. We have recently shown that this approach can also cure mouse prostate cancer, provided that it is combined with tumor-specific vaccination. Whether the response to alloantigens acts by providing helper function to enhance vaccine-specific responses or in other ways impinges on vaccine immunogenicity remains to be clarified, and this question is of clinical relevance. In this study, we have addressed this issue by comparing the immunogenicity of dendritic cells pulsed with a peptide derived from a tumor/viral model Ag in recipients of donor cells either syngeneic to the host or differing for either Y-encoded or multiple minor H antigens. We report that vaccination elicits comparable proliferation and differentiation of peptide-specific CD8+ T cells despite concurrent expansion and differentiation of minor H antigen-specific IFN-γ effector T cells. Depletion of alloreactive CD4+ T cells reduced alloreactivity but not vaccine-induced CD8+ T cell priming, suggesting that alloresponses do not provide helper functions in peripheral lymphoid tissues. Vaccine-mediated T cell priming was also preserved in the case of multiple minor H antigen disparities, prone to graft-versus-host disease. Thus, in the context of nonmyeloablative allotransplantation aimed at restoring an effective tumor-specific T cell repertoire, minor H antigen-specific T cells do not interfere with vaccine-induced T cell priming, supporting the notion that posttransplant vaccination is a valuable strategy to boost tumor and pathogen-specific protective immunity.

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“…Taken together, this phase 1/2 study provided the first evidence indicating that DC vaccination can be performed safely in allogeneic HCT setting. DC vaccination was also performed in a therapeutic setting in a patient suffering from recurrent CMV reactivation after a second HCT (77). As there was emerging viral resistance to the antiviral chemotherapy, DC cells were prepared from CD14 + monocytes isolated from the patients PB and loaded with CMV PP65 protein.…”

Section: Vaccination Trial In Allo-hctmentioning

confidence: 99%

Dendritic Cell Therapy in an Allogeneic-Hematopoietic Cell Transplantation Setting: An Effective Strategy toward Better Disease Control?

et al. 2014

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Hematopoietic cell transplantation (HCT) is a last treatment resort and only potentially curative treatment option for several hematological malignancies resistant to chemotherapy. The induction of profound immune regulation after allogeneic HCT is imperative to prevent graft-versus-host reactions and, at the same time, allow protective immune responses against pathogens and against tumor cells. Dendritic cells (DCs) are highly specialized antigen-presenting cells that are essential in regulating this balance and are of major interest as a tool to modulate immune responses in the complex and challenging phase of immune reconstitution early after allo-HCT. This review focuses on the use of DC vaccination to prevent cancer relapses early after allo-HCT. It describes the role of host and donor-DCs, various vaccination strategies, different DC subsets, antigen loading, DC maturation/activation, and injection sites and dose. At last, clinical trials using DC vaccination post-allo-HCT and the future perspectives of DC vaccination in combination with other cancer immunotherapies are discussed.

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Dendritic cell vaccination in an allogeneic stem cell recipient receiving a transplant from a human cytomegalovirus (HCMV)-seronegative donor: induction of a HCMV-specific Thelper cell response

Cited by 14 publications

References 19 publications

Rapid generation of NY-ESO-1-specific CD4⁺T_HELPER1 cells for adoptive T-cell therapy

Rapid generation of NY-ESO-1-specific CD4⁺T_HELPER1 cells for adoptive T-cell therapy

Concurrent Allorecognition Has a Limited Impact on Posttransplant Vaccination

Dendritic Cell Therapy in an Allogeneic-Hematopoietic Cell Transplantation Setting: An Effective Strategy toward Better Disease Control?

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Dendritic cell vaccination in an allogeneic stem cell recipient receiving a transplant from a human cytomegalovirus (HCMV)-seronegative donor: induction of a HCMV-specific Thelper cell response

Cited by 14 publications

References 19 publications

Rapid generation of NY-ESO-1-specific CD4+THELPER1 cells for adoptive T-cell therapy

Rapid generation of NY-ESO-1-specific CD4+THELPER1 cells for adoptive T-cell therapy

Concurrent Allorecognition Has a Limited Impact on Posttransplant Vaccination

Dendritic Cell Therapy in an Allogeneic-Hematopoietic Cell Transplantation Setting: An Effective Strategy toward Better Disease Control?

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Product

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Rapid generation of NY-ESO-1-specific CD4⁺T_HELPER1 cells for adoptive T-cell therapy

Rapid generation of NY-ESO-1-specific CD4⁺T_HELPER1 cells for adoptive T-cell therapy