Generation of a Novel Dendritic-cell Vaccine Using Melanoma and Squamous Cancer Stem Cells

Li, Qiao; Lü, Lin; Tao, Huimin; Xue, Carolyn; Teitz-Tennenbaum, Seagal; Owen, Jennifer C.; Moyer, Jeffrey S.; Prince, Mark E.; Chang, Alfred E.; Wicha, Max S.

doi:10.3791/50561

Cited by 11 publications

(12 citation statements)

References 9 publications

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“…An overview of to date known anti-cancer therapies including those targeting CSC is presented in the Table 2. Current studies are conducted at the University of Michigan towards developing an autologous CSC-based therapeutic vaccine for clinical use in an adjuvant setting [131]. There are hopes that the near future will bring novel diagnostic and therapeutic approaches that will result in significant improvement of OSCC management and patient outcome.…”

Section: Therapeutic Relevance Of Stem Cells Researchmentioning

confidence: 99%

Oral epithelial stem cells—Implications in normal development and cancer metastasis

Papagerakis

Pannone

Zheng

et al. 2014

Experimental Cell Research

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Oral mucosa is continuously exposed to environmental forces and has to be constantly renewed. Accordingly, the oral mucosa epithelium contains a large reservoir of epithelial stem cells necessary for tissue homeostasis. Despite considerable scientific advances in stem cell behavior in a number of tissues, fewer studies have been devoted to the stem cells in the oral epithelium. Most of oral mucosa stem cells studies are focused on identifying cancer stem cells (CSC) in oral squamous cell carcinomas (OSCCs) among other head and neck cancers. OSCCs are the most prevalent epithelial tumors of the head and neck region, marked by their aggressiveness and invasiveness. Due to their highly tumorigenic properties, it has been suggested that CSC may be the critical population of cancer cells in the development of OSCC metastasis. This review presents a brief overview of epithelium stem cells with implications in oral health, and the clinical implications of the CSC concept in OSCC metastatic dissemination.

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Section: Therapeutic Relevance Of Stem Cells Researchmentioning

confidence: 99%

Oral epithelial stem cells—Implications in normal development and cancer metastasis

Papagerakis

Pannone

Zheng

et al. 2014

Experimental Cell Research

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“…Recently, DC loading of cancer stem cell lysate was reported to be more effective than DCs loaded with unsorted total tumor lysate in the induction of antitumor immunity. Splenocytes isolated from the host vaccinated with DCs pulsed with unsorted total tumor lysate produced higher amount of IFN-γ and GM-CSF than splenocytes isolated from host vaccinated with DCs pulsed with unsorted total tumor lysate in murine melanoma and squamous cell cancer models [30]. Other approaches, including tumor cell RNA, apoptotic tumor cell, DC fusion to tumor cells, and tumorderived exosomes, have also been used for antigen-loading of DCs.…”

Section: Generation Of Tumor-specific T Cells With DC Vaccinesmentioning

confidence: 99%

Anticancer Dendritic Cell Vaccines Producing effective Antitumor T Cell Responses

Khansari¹

2017

IJVV

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In the past two decades, immunotherapy has been investigated as a novel modality in cancer therapy. The aim of immunotherapy is augmenting body's immune system to recognize and destroy malignant cells efficiently and safely. Dendritic cell (DC)-based vaccination is one of the most important approaches of cancer immunotherapy, in which autologous ex vivo generated tumor antigen-loaded DCs are injected to cancer patients in order to augment antitumor immunity. Various DC culture conditions, tumor antigen sources, antigen loading strategies, DC maturation stimuli, and routes of vaccination have been used to increase efficacy of DC vaccines. However, therapeutic efficacy of DC vaccines is still limited in cancer patients and preparation of clinical-grade DCs should be standardized to generate immuno stimulatory DCs and to prevent development of immunosuppressive DCs. Understanding DC function in triggering adaptive immunity or induction of immunological tolerance in cancer setting may be helpful in improving therapeutic efficacy of DC vaccines. In this article, we reviewed DCs interactions with T cells, efficacy of ex vivo generated DCs in triggering/suppression of antitumor effector T cell responses, as well as recent findings about DC vaccinations in cancer patients.

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“…In murine models of melanoma D5 and squamous cell cancer SCC7, enriched CSCs are immunogenic and significantly more effective as an antigen source in inducing antitumor immunity than unsorted tumor cells or purified non-CSCs (56,57). Likewise, a high expression level of ALDH (ALDH hi ) is also a specific marker for the CSC population in human head and neck squamous cell carcinoma (HNSCC).…”

Section: Targeted Therapy Against Other Cscsmentioning

confidence: 99%

“…Likewise, a high expression level of ALDH (ALDH hi ) is also a specific marker for the CSC population in human head and neck squamous cell carcinoma (HNSCC). When ALDH hi CSCs and cells with low levels of ALDH (ALDH lo ) were isolated from HNSCC, and effector T and B cells and dendritic cells (DCs) were generated from the patient peripheral blood mononuclear cells, immunization of DCs with ALDH hi CSCs was demonstrated to sensitize T and B cells to produce significantly higher amounts of interferon-γ, granulocyte-macrophage colony-stimulating factor, IgM and IgG, respectively, as compared with immunization with ALDH lo cells (57). These observations indicate that immunization of DCs with ALDH hi CSCs boosts cellular and humoral immunity against head and neck cancer, which may help develop novel approaches for head and neck cancer treatment by utilizing an autologous CSC-based vaccine to selectively and immunologically target CSCs.…”

Section: Targeted Therapy Against Other Cscsmentioning

confidence: 99%

Targeted therapy against cancer stem cells

Yang

Rycaj

2015

Oncology Letters

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Abstract. Research into cancer stem cells (CSCs), which have the ability to self-renew and give rise to more mature (differentiated) cancer cells, and which may be the cells responsible for the overall organization of a tumor, has progressed rapidly and concomitantly with recent advances in studies of normal tissue stem cells. CSCs have been reported in a wide spectrum of human tumors. Like normal tissue stem cells, CSCs similarly exhibit significant phenotypic and functional heterogeneity. The ability of CSCs to self-renew results in the immortality of malignant cells at the population level, whereas the ability of CSCs to differentiate, either fully or partially, generates the cellular hierarchy and heterogeneity commonly observed in solid tumors. CSCs also appear to have maximized their pro-survival mechanisms leading to their relative resistance to anti-cancer therapies and subsequent relapse. Studies in animal models of human cancers have also provided insight into the heterogeneity and characteristics of CSCs, helping to establish a platform for the development of novel targeted therapies against specific CSCs. In the present study, we briefly review the most recent progress in dissecting CSC heterogeneity and targeting CSCs in various human tumor systems. We also highlight a few examples of CSC-targeted drug development and clinical trials, with the ultimate aim of developing more effective therapeutic regimens that are capable of preventing tumor recurrence and metastasis. IntroductionThe etiology of cancer development and the molecular mechanisms underlying conventional therapy-resistant progression, metastasis and recurrence are poorly understood, resulting in numerous patients who still fail therapy. Cancer is recognized as a heterogeneous disease, an intrinsic attribute that contributes to therapy failure. Emerging evidence from a number of tumor systems has revealed the existence of distinct subpopulations of stem-like cancer cells, termed cancer stem cells (CSCs), that possess clonal long-term repopulation and self-renewal capacities. Theories suggest that both genetic and CSC models of cancer contribute to this tumor heterogeneity. With stemness as a guiding principle, data generated from advanced genome sequencing, epigenetics and the influences of non-tumor cell elements in the tumor microenvironment could potentially be combined in order to reveal the underlying mechanisms of tumor heterogeneity (1). As a fraction of this heterogeneous population, CSCs are inherently resistant to cytotoxic chemotherapy and radiation, and evidence has linked stemness to prognosis and therapy failure (2). This suggests that specifically identifying how CSC involvement is linked to tumor initiation, progression, metastasis and therapy resistance may lead to a more perceptive approach of developing therapeutics to target this cell population. Despite the vast complexity observed within a tumor, there are fundamental attributes of CSCs that may be exploited in drug development. A number of potential CSC therapeutic...

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Generation of a Novel Dendritic-cell Vaccine Using Melanoma and Squamous Cancer Stem Cells

Cited by 11 publications

References 9 publications

Oral epithelial stem cells—Implications in normal development and cancer metastasis

Oral epithelial stem cells—Implications in normal development and cancer metastasis

Anticancer Dendritic Cell Vaccines Producing effective Antitumor T Cell Responses

Targeted therapy against cancer stem cells

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