T-cell therapy after hematopoietic stem cell transplantation

Kennedy-Nasser, Alana A.; Brenner, Malcolm K.

doi:10.1097/moh.0b013e3282ef615a

Cited by 15 publications

(13 citation statements)

References 55 publications

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“…DLI with tumor-specific donor lymphocytes may be proven as one of the most effective approaches to separate GVT from GVHD. 97,98 The clinical observations that some patients experience GVT without GVHD as well as the possibility of preparing leukemia-specific lymphocytes suggest that such approaches to treatment is possible. However, the major limitation to tumor-specific DLI would be the difficulties in identifying and isolating tumor-specific target antigens.…”

Section: Gvhd and Gvl After DLImentioning

confidence: 99%

New strategies of DLI in the management of relapse of hematological malignancies after allogeneic hematopoietic SCT

Chang

Zang

Xia

2015

Bone Marrow Transplant

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DLI is an effective strategy for patients with recurrent hematological malignancies after allogeneic hematopoietic SCT (allo-HSCT). DLI has been widely applied to boost the graft vs tumor (GVT) or GVL effects. However, given the potentially severe complications associated with conventional DLI and transient GVL effect, new strategies for DLI are emerging. In this review, we have discussed the recent important studies on DLI as a prophylactic or therapeutic modality for relapsed hematological disorders after allo-HSCT. The strategies to separate GVL from GVHD have also been discussed. Leukemia-targeting therapy and lymphodepletion combined with DLI, and prophylactic DLI after allo-HSCT are often employed for patients with high risk of relapse, which has been reviewed as well. In addition, we have also discussed the issues on DLI to be further addressed, such as the doses, timing and frequency of DLI in different clinical settings, leukemic antigen-specific DLI as well as how to augment GVL effect while attenuating GVHD.

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Section: Gvhd and Gvl After DLImentioning

confidence: 99%

New strategies of DLI in the management of relapse of hematological malignancies after allogeneic hematopoietic SCT

Chang

Zang

Xia

2015

Bone Marrow Transplant

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“…The therapeutic benefit of allogeneic HSCT is largely related to graft-versus-tumor (GVT) effects mediated by donor-derived immunocompetent T cells present within the graft or infused to patients following HSCT, i.e., DLI (5). In recipients of genetically different but MHC-matched transplants, donor-derived T cells recognize tumor-associated antigens (TAA) favoring tumor eradication (6) and also host-specific histocompatibility (H) antigens (7).…”

Section: Introductionmentioning

confidence: 99%

Concomitant Tumor and Minor Histocompatibility Antigen–Specific Immunity Initiate Rejection and Maintain Remission from Established Spontaneous Solid Tumors

et al. 2010

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Nonmyeloablative hematopoietic cell transplantation can cure patients with hematologic malignancies but has reported limited success against solid tumors. This is possibly because of profound peripheral tolerance mechanisms and/or suboptimal tumor recognition by effector T lymphocytes. We report that in mice developing spontaneous prostate cancer, nonmyeloablative minor histocompatibility mismatched hematopoietic stem cell transplantation, and donor lymphocyte infusion of unmanipulated lymphocytes combined with posttransplant tumor-specific vaccination circumvents tumor-specific tolerance, allowing acute tumor rejection and the establishment of protective immunosurveillance. Although donor-derived tumor-specific T cells readily differentiated into effector cells and infiltrated the tumor soon after infusion, they were alone insufficient for tumor eradication, which instead required the concomitance of minor histocompatibiltiy antigen-specific CD8 + T-cell responses. The establishment of protective immunosurveillance was best induced by posttransplant tumor-specific vaccination. Hence, these results provide the proof of principle that tumor-specific T-cell responses have to be harnessed together with minor histocompatibility responses and sustained by posttransplant tumor-specific vaccination to improve the efficacy of allotransplantion for the cure of solid tumors.

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“…[1][2][3][4][5][6] In mice and humans, antigen (Ag) restimulation with vaccination after ACT significantly potentiates the in vivo antitumor efficacy of adoptively transferred self-/tumor-reactive CD8 ϩ T cells. [7][8][9][10][11][12] Efficient translation of this approach to human trials has been limited by a number of technical challenges.…”

Section: Introductionmentioning

confidence: 99%

Programming tumor-reactive effector memory CD8+ T cells in vitro obviates the requirement for in vivo vaccination

Klebanoff

Hwang

et al. 2009

Blood

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T-cell therapy after hematopoietic stem cell transplantation

Abstract: In this review we describe current strategies for adoptive T-cell immunotherapy after hematopoietic stem cell transplantation.

Cited by 15 publications

References 55 publications

New strategies of DLI in the management of relapse of hematological malignancies after allogeneic hematopoietic SCT

New strategies of DLI in the management of relapse of hematological malignancies after allogeneic hematopoietic SCT

Concomitant Tumor and Minor Histocompatibility Antigen–Specific Immunity Initiate Rejection and Maintain Remission from Established Spontaneous Solid Tumors

Programming tumor-reactive effector memory CD8+ T cells in vitro obviates the requirement for in vivo vaccination

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