T-regulatory cells are relatively deficient in squamous carcinomas undergoing regression in mice immunized with a squamous carcinoma vaccine enriched for immunotherapeutic cells

Chopra, Amla; O-Sullivan, InSug; Carr, Janai R.; Kim, T S; Cohen, Edward P.

doi:10.1038/sj.cgt.7701040

Cited by 3 publications

(4 citation statements)

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“…The KLN 205 cell line has been applied in around 100 published research studies. While morphologically it seems non-negotiable that KLN 205 in culture appears similar to SCC cells [12][13][14]24,25] , they have been applied as models for lung cancer in general [15][16][17][18][19][20][21][22] , metastatic lung cancer cells [26] and even non-small cell lung cancer [23] . Surprisingly, they have even worked as a model for tongue cancer [27] and subcutaneous SCC [28] .…”

Section: Discussionmentioning

confidence: 99%

“…In addition, it has been shown that the patterns of gains and losses in human lung cancer (SCC-type) and human small cell lung cancer type are strikingly similar as well [31] . Thus, their use as models for SCC cells in general [12][13][14]24,25] or even for subcutaneous SCC [28] seems to be justifiable. In addition, considering their genetic background, KLN 205 can use as a model for lung cancer in general [15][16][17][18][19][20][21][22] , as as well as for even non-small cell lung cancer [23] .…”

Section: Discussionmentioning

confidence: 99%

“…• SCC [12][13][14] • Lung cancer [15][16][17][18][19][20][21][22] • Non-small cell lung cancer [23] • L-SCC [24,25] • Lung-metastatic tumour cells [26] • Tongue cancer [27] • Subcutaneous SCC [28] It was shown previously that a comprehensive molecular cytogenetic characterisation of murine tumour cell lines can define the cancer subtype to which they belong because the cytogenomic profile of chromosomal imbalances is typically specific to a certain tumour type [6] . Thus, the karyotype, a comprehensive map of chromosomal imbalances, and an in silico translation of these results to the human genome were performed here for the KLN 205 cell line to possibly determine to which human cancer type it is most similar.…”

Section: Introductionmentioning

confidence: 99%

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First molecular cytogenetic characterisation of tracheal squamous cell carcinoma cell line KLN 205

Azawi¹,

Liehr²,

Rinčić³

2021

JCMT

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Aim: Murine tumour cell lines have been used in thousands of studies. Strikingly, it is rather the rule than exception for most of them that not much is known about their genetic characteristics. The squamous cell carcinoma (SCC) cell line KLN 205 is such an example. KLN 205 cells have not been studied yet for karyotype or acquired copy number variations (CNVs), but they have been used as models for (metastatic) lung cancer, lung-SCC, non-small cell lung cancer, tongue cancer and subcutaneous SCC. Here, it was characterised cytogenomically for the first time. Methods:The cell line KLN 205 was characterised comprehensively by molecular cytogenetics using multicolour banding as well as molecular karyotyping. Based on these results, a map of the imbalances and breakpoints determined in the murine genome was translated to the human genome.Results: Here, it could be shown that this > 40-year-old cell line has a stable, approximately tetraploid karyotype comprising 77-82 chromosomes. However, there are few structural chromosomal aberrations: only six derivatives involving chromosomes 2, 3, 5, 9, 10 and/or 19 could be found. According to the literature, SCCs derived from different human tissues, as well as lung SCC and non-small cell lung cancer, display overall similar CNV patterns. Conclusion:Thus, according to the genetic profile found here, KLN 205 can be applied as a general model for human SCC; it is also suited as a model for lung cancer in general. Further molecular genetic characterisation of KLN 205 cell line may find more lung-and/or SCC-specific alterations.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

First molecular cytogenetic characterisation of tracheal squamous cell carcinoma cell line KLN 205

Azawi¹,

Liehr²,

Rinčić³

2021

JCMT

View full text Add to dashboard Cite

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“…T-cell mediated anti tumor immunity appears to be specific and mainly driven by CD8 T-cells. Regulatory T-cells are down-regulated by DNA-based vaccines as indicated by the reduction in the relative numbers of cells that express CD4/CD25, CD62L and Fox P3 [10,12] in the regressing tumors.…”

Section: Introductionmentioning

confidence: 99%

Tumor-DNA Based Vaccines Fail to Induce Autoimmune Disease in Mice

O-Sullivan¹,

Lichtor

Glick

et al. 2010

TOCIJ

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Allogeneic cellular cancer vaccines that express tumor antigens specified by tumor-DNA have been found to be effective in the treatment of mice with intracerebral breast cancer, a metastasis model system. The vaccines were prepared by the transfer of genomic DNA from a spontaneously arising adenocarcinoma of the mammary gland into a mouse fibroblast cell line (LM). The immunity in tumor-bearing mice treated by immunization with the DNA-based vaccines was specific for the type of tumor from which the DNA was obtained. It was driven mainly by CD8+ T-cells. Here, we present data indicating that animals receiving the therapeutic vaccines failed to exhibit signs of autoimmunity, as indicated by an examination of various H/E stained organs and tissues including brain for infiltrating inflammatory cells and by the absence of serum anti-nuclear antibody (ANA) in the immunized mice. In addition, tumors derived from the vaccine itself failed to develop in immune-competent tumor-free mice injected with the non-irradiated allogeneic vaccines alone.

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Enhancing Cellular Cancer Vaccines

et al. 2009

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Various strategies have been used to generate cellular cancer vaccines with the expectation that they will become an effective part of the overall management of cancer patients. However, with few notable exceptions, immunization has not resulted in significant long-term therapeutic benefits. Tumor growth has continued and patient survival has been at best only modestly prolonged. One possible explanation is that as only a small proportion of the constituents of malignant cells are 'tumor specific' and the vast majority are the products of nonantigenic, normal 'housekeeping' genes, the immune response in patients immunized with cellular cancer vaccines is not sufficient to result in tumor rejection. Here, we review and characterize various types of cellular cancer vaccines. In addition, in a mouse breast cancer model system, we describe a unique strategy designed to enrich cellular vaccines for cells that induce tumor immunity. Numerous advantages and disadvantages of cancer immunotherapy with cellular vaccines are also presented. Keywordscancer vaccine; dendritic cell; dNA vaccine; enriched vaccine; fibroblast; leukapheresis; tumor dNA Numerous attempts have been made to prepare effective cancer vaccines that can be used to treat cancer patients in the expectation that the anti-tumor immune response will result in tumor regression [1][2][3][4][5][6][7][8][9]. The underlying rationale is that the antigenic phenotype of cells in the tumor differs from that of normal, nonmalignant cells in the patient. The immunity to unique antigens expressed by the malignant cells, which is induced by the vaccine, would, in theory, result in the selective killing of the patient's malignant cells only. However, relatively few antigenic determinants expressed by cancer cells are 'tumor specific. With few exceptions, the vast majority of determinants expressed by the patient's tumor are presented by normal, nonmalignant cells as well. MUC1 is a notable example. MUC1 is a heavily glycosylated glycoprotein associated with both normal and malignant cells. Its expression by cancer cells, specified by a mutant/dysregulated gene, is aberrant in the sense that the glycosylation pattern of the molecule is altered [10][11][12]. The altered glycosylation pattern renders the molecule antigenic. Other examples of dysregulated genes that specify tumor antigens include Her2/neu in breast cancer and KRAS in colon cancer [13][14][15][16][17]. In these instances, the density of the molecules expressed by the malignant cells is greater than that of normal cells. By contrast, cancer caused by oncogenic viruses express determinants specific to the virus. Cervical cancer caused by the human papillomavirus is a notable example. The malignant, virally infected cells express antigenic determinants specific to the papillomavirus. The products of the virally associated E6 and E7 genes are tumor specific [18][19][20]. The Epstein-Barr virus nuclear

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T-regulatory cells are relatively deficient in squamous carcinomas undergoing regression in mice immunized with a squamous carcinoma vaccine enriched for immunotherapeutic cells

Cited by 3 publications

References 48 publications

First molecular cytogenetic characterisation of tracheal squamous cell carcinoma cell line KLN 205

First molecular cytogenetic characterisation of tracheal squamous cell carcinoma cell line KLN 205

Tumor-DNA Based Vaccines Fail to Induce Autoimmune Disease in Mice

Enhancing Cellular Cancer Vaccines

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