Adoptive cellular immunotherapy for childhood malignancies

Cooper, Laurence J.N.

doi:10.1038/sj.bmt.1705930

Cited by 7 publications

(5 citation statements)

References 140 publications

(120 reference statements)

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“…Various concepts and strategies were introduced and discussed regarding the adoptive transfer of various kinds of immune cells, mainly focusing on cancers such as breast (29), prostate (30) and ovarian cancer (31). In addition, adoptive immunotherapies were further investigated for melanoma (32), pediatric malignancies (33), thyroid carcinoma (34) and renal cell malignancies (35).…”

Section: Discussionmentioning

confidence: 99%

Efficacy of ex vivo activated and expanded natural killer cells and T lymphocytes for colorectal cancer patients

Baskar¹,

Pullai²,

Krishnan³

et al. 2014

Biomedical Reports

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Immune cell-based therapies using natural killer (NK) cells and cytotoxic T cells are under constant scrutiny, with the aim to design an effective and reduced-toxicity therapy, which will benefit patients via improved quality of life and improved prognosis. Four patients with stage IV colon cancer were administered 1, 3, 5 and 6 effector cell intravenous infusions, respectively. Peripheral blood was collected from the patients and the activation and expansion of NK and T cells was performed in Good Manufacturing Practice-certified clean rooms for ~12-15 days. Immunophenotypic analysis of the peripheral blood mononuclear cells (PBMCs) and expanded NK and T cells was conducted using flow cytometry and the patients were followed up. On average, 4.8×10 initial PBMCs and 2.7×10 total expanded cells were obtained. The intravenous infusions of the expanded cells were not accompanied by adverse reactions. Improved prognosis, reflected by a considerable decrease in the cancer markers, accompanied by an improved quality of life in the patients were observed. In conclusion, potential strategies are currently under development for the large-scale production of effectors cells; therefore, autologous immune enhancement therapy (AIET) may be considered as a viable approach to cancer treatment.

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Section: Discussionmentioning

confidence: 99%

Efficacy of ex vivo activated and expanded natural killer cells and T lymphocytes for colorectal cancer patients

Baskar¹,

Pullai²,

Krishnan³

et al. 2014

Biomedical Reports

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“…Reconstituting or increasing cellular immunity can be achieved through the infusion of tumor-specific T cells. Autologous CD4 + or CD8 + T cells can be manipulated ex vivo in various ways to obtain high numbers of clinical grade tumor-specific T cells [ 23 ]. The therapeutic effect of infused tumor-specific T cells depends on the viability of the cells, their homing to the tumor, and their ability to kill within the tumor microenvironment.…”

Section: Immunotherapy Strategies In Pediatric Cancer Patientsmentioning

confidence: 99%

Targets for active immunotherapy against pediatric solid tumors

Jacobs

Coulie

Figdor

et al. 2008

Cancer Immunol Immunother

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The potential role of antibodies and T lymphocytes in the eradication of cancer has been demonstrated in numerous animal models and clinical trials. In the last decennia new strategies have been developed for the use of tumor-speciWc T cells and antibodies in cancer therapy. EVective anti-tumor immunotherapy requires the identiWcation of suitable target antigens. The expression of tumorspeciWc antigens has been extensively studied for most types of adult tumors. Pediatric patients should be excellent candidates for immunotherapy since their immune system is more potent and Xexible as compared to that of adults. So far, these patients do not beneWt enough from the progresses in cancer immunotherapy, and one of the reasons is the paucity of tumor-speciWc antigens identiWed on pediatric tumors. In this review we discuss the current status of cancer immunotherapy in children, focusing on the identiWcation of tumor-speciWc antigens on pediatric solid tumors.

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“…For adoptive therapy experiments, sublethally irradiated NOD-SCIDb 2 m −/mice were implanted subcutaneously into the flank with 2.5 × 10 6 pp65/IE-transduced HLA-A * 0201 + or HLA-A * 0201 − EBV cell lines and treated 5 days later with three weekly peritumoral injections of equal numbers of anti-CMVpp65 or anti-Flu purified CD8 T cells (1-5 × 10 6 cells), generated in vitro from HLA-A0201+ PBMC after one or two rounds of stimulation(s) with the peptide-loaded pDC line. Tumor size was monitored every 2-3 days and tumor volume calculated using the formula: (short diameter) 2 xlong diameter/2. Specific T cells were analyzed in tumor and spleencell suspensions by tetramer labeling and flow cytometry analysis.…”

Section: In Vivo Functional Assays In Humanized Micementioning

confidence: 99%

“…Epstein-Barr virus (EBV) lymphoproliferative disease and opportunistic infections such as CMV represent a major cause of hematopoietic stem cell (HSCT) and solid organ (SOT) transplantation failure, morbidity and mortality. To treat these diseases, which are often refractory to conventional chemotherapy, radiotherapy or antiviral treatments, adoptive transfer of antigen-specific T lymphocytes appears to be an emerging and successful immunotherapeutic strategy (1)(2)(3).…”

Section: Introductionmentioning

confidence: 99%

Induction of Antiviral Cytotoxic T Cells by Plasmacytoid Dendritic Cells for Adoptive Immunotherapy of Posttransplant Diseases

Aspord

Laurin

Richard

et al. 2011

American Journal of Transplantation

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Virus-associated hematologic malignancies (EBV lymphoproliferative disease) and opportunistic infections (CMV) represent a major cause of hematopoietic stem cell and solid organ transplantation failure. Adoptive transfer of antigen-specific T lymphocytes appears to be a major and successful immunotherapeutic strategy, but improvements are needed to reliably produce high numbers of virus-specific T cells with appropriate requirements for adoptive immunotherapy that would allow extensive clinical use. Since plasmacytoid dendritic cells (pDCs) are crucial in launching antiviral responses, we investigated their capacity to elicit functional antiviral T-cell responses for adoptive cellular immunotherapy using a unique pDC line and antigens derived from Influenza, CMV and EBV viruses. Stimulation of peripheral blood mononuclear cells from HLA-A * 0201 + donors by HLA-A0201 matched pDCs pulsed with viral-derived peptides triggered high levels of multi-specific and functional cytotoxic T-cell responses (up to 99% tetramer + CD8 T cells) in vitro. Furthermore, the central/effector memory cytotoxic T cells elicited by the pDCs strongly display antiviral activity upon adoptive transfer into a humanized mouse model that mimics a virus-induced malignancy. We provide a simple and potent method to generate virus-specific CTL with the required properties for adoptive cellular immunotherapy of post-transplant diseases.

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Adoptive cellular immunotherapy for childhood malignancies

Cited by 7 publications

References 140 publications

Efficacy of ex vivo activated and expanded natural killer cells and T lymphocytes for colorectal cancer patients

Efficacy of ex vivo activated and expanded natural killer cells and T lymphocytes for colorectal cancer patients

Targets for active immunotherapy against pediatric solid tumors

Induction of Antiviral Cytotoxic T Cells by Plasmacytoid Dendritic Cells for Adoptive Immunotherapy of Posttransplant Diseases

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