Review Immunotargeting of cancer stem cells

Kwiatkowska-Borowczyk, Eliza; Gąbka-Buszek, Agnieszka; Jankowski, Jakub; Maćkiewicz, Andrzej

doi:10.5114/wo.2014.47129

Cited by 29 publications

(28 citation statements)

References 67 publications

(50 reference statements)

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“…CSCs are involved in tumor recurrence and metastasis, and are resistant to conventional therapies, such as chemo-or radiotherapy. Accordingly, they are the targets for novel therapeutic strategies, including immunotherapies [3].…”

Section: Introductionmentioning

confidence: 99%

Novel Genetic Melanoma Vaccines Based on Induced Pluripotent Stem Cells or Melanosphere-Derived Stem-Like Cells Display High Efficacy in a murine Tumor Rejection Model

Gąbka-Buszek

Kwiatkowska-Borowczyk

Jankowski

et al. 2020

Vaccines

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Therapeutic cancer vaccines have elicited renewed interest due to the development of immune checkpoint inhibitors. The role of these vaccines is to induce specific effector cells for killing cancer cells. Cancer stem cells (CSCs) are responsible for tumor growth and progression. Accordingly, they are targets for various cancer therapies, including immunotherapy. Here, we demonstrate the effectiveness of melanoma vaccines composed of genetically modified tumor cells admixed with melanoma stem-like cells (MSC) or induced pluripotent stem cells (iPSCs). Two vaccines were constructed. The first vaccine contained cells derived from B16F10 melanospheres (SFs) with CSC characteristics. The second vaccine contained syngeneic murine induced pluripotent stem cells (miPSCs). iPSCs or SF cells were admixed with B16F10 cells, modified with the designer cytokine Hyper-IL6(H6) (B16/H6). Control mice received B16/H6 cells, B16F10 cells or PBS. Immunization with either vaccine significantly inhibited tumor growth and increased disease-free survival (DFS) and overall survival (OS) in C57BL/6 mice. Mice treated with the SF or iPSC vaccine demonstrated increased activation of the immune response in the vaccination site and tumor microenvironment compared to those treated with B16/H6, B16F10 or PBS. Higher infiltration of dendritic cells (DCs) monocytes, and natural killer (NK) cells; lower numbers of myeloid-derived suppressor cells (MDSCs) and regulatory T cells (Tregs); higher levels of the cytokines INFγ and IL-12 were observed with the novel vaccines than with the control treatments. In vitro restimulation of splenocytes derived from mice immunized with B16F10 cell, SF cell or miPSC lysates increased the proliferation of CD4+ T helper lymphocytes and secretion of cytokines. An increased serum titer of antibodies directed against B16F10 cells was found in mice immunized with the SF vaccine. The most effective DFS and OS extensions were reached with the miPSCs vaccine. The described results form the basis for a novel platform for the next generation of cancer vaccines composed of allogeneic cancer-specific cells modified with a molecular adjuvant gene and admixed with allogeneic miPSCs or SFs.

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Section: Introductionmentioning

confidence: 99%

Novel Genetic Melanoma Vaccines Based on Induced Pluripotent Stem Cells or Melanosphere-Derived Stem-Like Cells Display High Efficacy in a murine Tumor Rejection Model

Gąbka-Buszek

Kwiatkowska-Borowczyk

Jankowski

et al. 2020

Vaccines

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“…Almost a century ago, Otto Warburg determined that oncogenic cells preferentially use glycolysis and lactic acid fermentation to produce energy in contrast to the low glycolytic rates in healthy cells . With the developments of new biochemical and molecular biological tools, our understanding of how onco‐proteins can promote tumorigenesis by interfering with cellular bioenergetics has significantly increased and led to a revival in the field of cancer metabolic research . As such, mutations in the genes encoding the metabolic enzymes isocitrate dehydrogenase (IDH) 1 and 2 have been discovered as positive prognostic markers in GBMs .…”

mentioning

confidence: 99%

Targeting cancer stem‐like cells in glioblastoma and colorectal cancer through metabolic pathways

Kahlert

Mooney

Natsumeda

et al. 2016

Intl Journal of Cancer

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Cancer stem-like cells (CSCs) are thought to be the main cause of tumor occurrence, progression and therapeutic resistance. Strong research efforts in the last decade have led to the development of several tailored approaches to target CSCs with some very promising clinical trials underway; however, until now no anti-CSC therapy has been approved for clinical use. Given the recent improvement in our understanding of how onco-proteins can manipulate cellular metabolic networks to promote tumorigenesis, cancer metabolism research may well lead to innovative strategies to identify novel regulators and downstream mediators of CSC maintenance. Interfering with distinct stages of CSC-associated metabolics may elucidate novel, more efficient strategies to target this highly malignant cell population. Here recent discoveries regarding the metabolic properties attributed to CSCs in glioblastoma (GBM) and malignant colorectal cancer (CRC) were summarized. The association between stem cell markers, the response to hypoxia and other environmental stresses including therapeutic insults as well as developmentally conserved signaling pathways with alterations in cellular bioenergetic networks were also discussed. The recent developments in metabolic imaging to identify CSCs were also summarized. This summary should comprehensively update basic and clinical scientists on the metabolic traits of CSCs in GBM and malignant CRC.

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“…Preclinical studies have shown that CSC are immunogenic and a more effective antigen source for inducing protective antitumor immunity in mice than unselected tumor cells (3). Several clinical trials in which CSC lysate or mRNA are used to pulse or transfect autologous dendritic cells (DC), that are then injected back into the patients, are currently underway in various tumor settings (4). However, this technique presents the difficulty of setting up standardized functional DC production procedures (5).…”

Section: Introductionmentioning

confidence: 99%

Immunotargeting of Antigen xCT Attenuates Stem-like Cell Behavior and Metastatic Progression in Breast Cancer

Lanzardo

Conti

Rooke³

et al. 2016

Cancer Research

138

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Resistance to therapy and lack of curative treatments for metastatic breast cancer suggest that current therapies may be missing the subpopulation of chemoresistant and radioresistant cancer stem cells (CSC). The ultimate success of any treatment may well rest on CSC eradication, but specific anti-CSC therapies are still limited. A comparison of the transcriptional profiles of murine Her2 þ breast tumor TUBO cells and their derived CSC-enriched tumorspheres has identified xCT, the functional subunit of the cystine/glutamate antiporter system x c À , as a surface protein that is upregulated specifically in tumorspheres. We validated this finding by cytofluorimetric analysis and immunofluorescence in TUBO-derived tumorspheres and in a panel of mouse and human triple negative breast cancer cell-derived tumorspheres. We further show that downregulation of xCT impaired tumorsphere generation and altered CSC intracellular redox balance in vitro, suggesting that xCT plays a functional role in CSC biology. DNA vaccination based immunotargeting of xCT in mice challenged with syngeneic tumorsphere-derived cells delayed established subcutaneous tumor growth and strongly impaired pulmonary metastasis formation by generating anti-xCT antibodies able to alter CSC self-renewal and redox balance. Finally, anti-xCT vaccination increased CSC chemosensitivity to doxorubicin in vivo, indicating that xCT immunotargeting may be an effective adjuvant to chemotherapy. Cancer Res; 76(1); 62-72. Ó2015 AACR.

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Review Immunotargeting of cancer stem cells

Cited by 29 publications

References 67 publications

Novel Genetic Melanoma Vaccines Based on Induced Pluripotent Stem Cells or Melanosphere-Derived Stem-Like Cells Display High Efficacy in a murine Tumor Rejection Model

Novel Genetic Melanoma Vaccines Based on Induced Pluripotent Stem Cells or Melanosphere-Derived Stem-Like Cells Display High Efficacy in a murine Tumor Rejection Model

Targeting cancer stem‐like cells in glioblastoma and colorectal cancer through metabolic pathways

Immunotargeting of Antigen xCT Attenuates Stem-like Cell Behavior and Metastatic Progression in Breast Cancer

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