Wilms’ tumor 1-specific cytotoxic T lymphocytes can be expanded from adult donors and cord blood

Krishnadas, Deepa K.; Stamer, Mindy; Dunham, Kimberly; Bao, Lei; Lucas, Kenneth G.

doi:10.1016/j.leukres.2011.06.037

Cited by 7 publications

(3 citation statements)

References 29 publications

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“…Hence, to reduce the risk of unwanted alloreactivity, antigen-specific cells could be positively selected after priming. This could be achieved either by recombinant MHC molecules conjugated to peptide of choice (tetramers/pentamers) or by HLA-independent procedures like the IFNγ-and CD137-capture techniques, the later having been successfully used in CB transplantation (171,(360)(361)(362). It remains to be seen whether cells expanded using our protocol may be stimulated to also respond to viral antigens or whether viral antigen priming is required before expansion as has been reported by Hanley et al (298).…”

Section: Further Tweaking Of the Expanded Product And Other Possibilimentioning

confidence: 83%

Expansion of T-cells from the cord blood graft as a predictive tool for complications and outcome of cord blood transplantation

Gertow¹,

Berglund²,

Okas³

et al. 2012

Clinical Immunology

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Section: Further Tweaking Of the Expanded Product And Other Possibilimentioning

confidence: 83%

Expansion of T-cells from the cord blood graft as a predictive tool for complications and outcome of cord blood transplantation

Gertow¹,

Berglund²,

Okas³

et al. 2012

Clinical Immunology

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“…In this way, it may also affect the tumor microenvironment enabling better migration and CTL function of the DC generated CTLs. The use of PBSC or BM as HCT graft has the obvious advantage that DLI can be performed as a prophylaxis or therapy combined with DC vaccination (4, 86, 87). Another possibility is the use TCR gene transfer for the formation of a large population of tumor-antigen-specific T cells that would reduce the risk of GvHD or other bystander immune responses (88, 89).…”

Section: Combination Therapiesmentioning

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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“…Tumor antigen–specific CTL can be generated by cloning, 19,20 sequential stimulation of T cells using antigen-pulsed autologous dendritic cells (DC), and by selection of activated cells based on interferon-γ (IFN-γ) secretion 21 or CD137 expression. 22,23 Once tumor antigen-specific CTLs have been generated in vitro, there is no well-defined eligibility requirements or criteria to qualify these CTLs for adoptive immunotherapy. It is not known whether antigen-specific T cells that make cytokines in response to an antigen are also capable of killing tumor cells bearing these target antigens, particularly after these CTLs are infused for cancer immunotherapy.…”

Section: Introductionmentioning

confidence: 99%

Expansion of cancer germline antigen–specific cytotoxic T lymphocytes for immunotherapy

et al. 2017

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The cancer germline antigens MAGE-A1, MAGE-A3, and NY-ESO-1 can be used to target relapsed or therapy-resistant malignant solid tumors, and previous studies have demonstrated that these antigens can be epigenetically upregulated on the surface of tumor cells following exposure to low-dose demethylating chemotherapy agents, such as decitabine. The extent to which cancer germline antigen cytotoxic T lymphocytes can be reliably expanded from healthy donors has not been well characterized, specifically in terms of whether these T cells consistently kill antigen-bearing targets or simply produce interferon-γ in the presence of the antigen. Cancer germline antigen cytotoxic T lymphocytes were generated using conventional method and high-density lymphocyte culture method. We demonstrate that there is no difference in the extent of antigen-specific killing with or without CD25 depletion when interleukin-21 is added to the cultures. Cancer germline antigen-specific killer cells could be expanded from 8/12 healthy donors using overlapping peptide mixes derived from MAGE-A1, MAGE-A3, and NY-ESO-1 and from 7/9 healthy donors using HLA-restricted epitopes. Furthermore, cytotoxic T lymphocyte derived from 4/5 patients displayed specific cytotoxicity of target cells expressing respective cancer germline antigen and HLA partially matched tumor lines. High-density lymphocyte culture prior to stimulation with cancer germline antigen peptides resulted in antigen-specific cytotoxic T lymphocyte from healthy donors and patients from whom cancer germline antigen cytotoxic T lymphocyte culture with conventional methods was not feasible. These data demonstrate that MAGE-A1-, MAGE-A3-, and NY-ESO-1-specific T cells with antigen-specific cytotoxicity can be cultured from healthy donors and patient-derived cells making adoptive immunotherapy with these cytotoxic T lymphocyte feasible.

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Wilms’ tumor 1-specific cytotoxic T lymphocytes can be expanded from adult donors and cord blood

Cited by 7 publications

References 29 publications

Expansion of T-cells from the cord blood graft as a predictive tool for complications and outcome of cord blood transplantation

Expansion of T-cells from the cord blood graft as a predictive tool for complications and outcome of cord blood transplantation

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

Expansion of cancer germline antigen–specific cytotoxic T lymphocytes for immunotherapy

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