Induction of Tumour Immunity with Tumour Cells Treated with Iodoacetate

Nature ◽  
1966 ◽  
Vol 209 (5024) ◽  
pp. 694-696 ◽  
Author(s):  
CHARLES A. APFFEL ◽  
BARRY G. ARNASON ◽  
JOHN H. PETERS
Keyword(s):  
Tumour Cells ◽  
Tumour Immunity

scholarly journals Evaluation of a canine transmissible venereal tumour cell line with tumour immunity capacity but without tumorigenic property

2019 ◽  
Vol 63 (2) ◽  
pp. 225-233 ◽  
Author(s):  
Yareellys Ramos Zayas ◽  
Moisés Armides Franco Molina ◽  
Reyes Tamez Guerra ◽  
Cristina Rodríguez Padilla
Keyword(s):  
Cell Line ◽  
Financial Burden ◽  
Morphological Characteristics ◽  
Tumour Cells ◽  
Tumour Cell Line ◽  
Histopathological Analysis ◽  
Isolated Cells ◽  
Tumour Immunity ◽  
Canine Transmissible Venereal Tumour ◽  
Transmissible Venereal Tumour

AbstractIntroduction:Canine transmissible venereal tumour (CTVT) is a sexually transmitted tumour affecting dogs worldwide, imposing a financial burden on dog owners. A stable culture cell line in continuous passages for >18 months has only been achieved once. The present study investigated a stable CTVT cell line isolated from a bitch and its potential as a vaccine.Material and Methods:A biopsy from a 2-year-old mongrel bitch with CTVT was obtained for histopathological confirmation and isolation of tumour cells. The isolated cells were cultured to passage 55 and characterised by flow cytometry, with karyotyping by GTG-banding and by PCR detection of myc S-2 and LINE AS1. The isolated CTVT cell line was also used as a preventive vaccine in a canine model.Results:Histopathological analysis of the isolated tumour cells revealed typical CTVT characteristics. Constant proliferation and stable morphological characteristics were observed during culture. Phenotypic analysis determined the expression of HLA-DR+, CD5.1+, CD14+, CD45+, CD83+, CD163+, and Ly-6G-Ly-6C+. GTG-banding revealed a mean of 57 chromosomes in the karyotype with several complex chromosomal rearrangements. LINE-c-myc insertion in the isolated CTVT cell line at 550 bp was not detected. However, a 340-bp band was amplified. Isolated CTVT cell line inoculation at a concentration of 1×108did not induce tumour growth in bitches, nor did a challenge with primary CTVT cells.Conclusion:The present study successfully identified and isolated a stable CTVT cell line that may be useful in CTVT prevention.

Tumour Immunity induced in Mice with Cell-free Homogenates of Influenza Virus-infected Tumour Cells

Nature ◽  
1971 ◽  
Vol 231 (5300) ◽  
pp. 265-266 ◽  
Author(s):  
C. BOONE ◽  
K. BLACKMAN ◽  
P. BRANDCHAFT
Keyword(s):  
Influenza Virus ◽  
Tumour Cells ◽  
Tumour Immunity

Heated tumour cells of autologous and allogeneic origin elicit anti-tumour immunity

2004 ◽  
Vol 53 (4) ◽  
pp. 323-330 ◽  
Author(s):  
Diane Soars ◽  
Angus G. Dalgleish ◽  
Alan A. Melcher ◽  
Hardev S. Pandha ◽  
Stephen M. Todryk ◽  
...  
Keyword(s):  
Tumour Cells ◽  
Tumour Immunity

Induction of Tumour Immunity with Tumour Cells treated with Extract of Garlic (Allium sativum)

Nature ◽  
1967 ◽  
Vol 216 (5110) ◽  
pp. 83-84 ◽  
Author(s):  
MOTONORI FUJIWARA ◽  
TOSHIKAZU NATATA
Keyword(s):  
Allium Sativum ◽  
Tumour Cells ◽  
Tumour Immunity

scholarly journals Exploration of nilotinib enhancing the anti-leukaemic effects of Gas6 deletion in Ph+ B-ALL by inducing immunogenic cell death

2021 ◽  
Author(s):  
◽  
Carolin Wachtel
Keyword(s):  
Immune Response ◽  
Cell Death ◽  
Fusion Gene ◽  
Philadelphia Chromosome ◽  
Chemotherapeutic Agents ◽  
Tumour Cells ◽  
Immunogenic Cell Death ◽  
Tumour Immunity

Cancer is the major cause of death besides cardiovascular disease. Leukaemia represents the most prevalent malignancy in children with a frequency of 30 % and is one of the ten leading types of cancer in adults. Philadelphia Chromosome-positive B-ALL (Ph+ B-ALL) is driven by the cytogenetic aberration of the reciprocal chromosomal translocation t(9;22)(q34;q11) leading to the formation of the Philadelphia chromosome with a BCR-ABL1 fusion gene. This fusion gene encodes a BCR-ABL1 oncoprotein which is characterized by a constitutively enhanced tyrosine kinase activity promoting amplified proliferation, differentiation arrest and resistance to cell death. Ph+ B-ALL is considered the most aggressive ALL subtype with a long-term survival rate in the range of only 30 % despite intensive standard of care including chemotherapy in combination with a tyrosine kinase inhibitor (TKI) followed by allogeneic stem cell transplantation after remission for clinically fit patients. The efficacy of chemotherapy has long been mainly attributed to tumour cell toxicity while immune modulating effects have been overlooked, especially in light of known immunosuppressive properties. Accumulative evidence, however, emphasizes the ability of chemotherapeutic agents, including TKIs, to normalise or re-educate a dysfunctional tumour microenvironment (TME) resulting in enhanced anti-tumour immunity. One of the underlying mechanisms of immune modulation is the induction of immunogenic cell death (ICD). ICD is an anti-tumour agent-induced cell death modality determined by the capacity to convert cancer cells into anti-cancer vaccines. The induction of ICD relies on the release of damage-associated molecular patterns (DAMPs) from dying tumour cells succumbing to ICD. Translocation of CALR to the cell surface, extracellular secretion of ATP and release of HMGB1 from the nucleus are key hallmarks of ICD that mediate anti-tumour immunity upon binding to antigen presenting cells resulting in a tumour antigen-specific immune response. Besides these molecular determinants, ICD is functionally defined by the inhibition of tumour growth in a vaccination assay in which mice are injected with tumour cells exposed to the potential ICD inducer in-vitro and then re-challenged with live tumour cells of the same cancer type. Both molecular and functional criteria determine the gold standard approach to assess ICD. By increasing the immunogenicity of cancer cells, ICD contributes to the restoration of immunosurveillance as an essential feature of tumour rejection, which is clinically reflected by improved therapeutic efficacy and disease outcome in patients. Therefore, identifying novel ICD inducers is an objective of interest in the context of cancer therapy. In respect of these considerations, the aim addressed in the present work is the examination of the second-generation TKI Nilotinib for the ability to induce ICD. The thesis is set in the context of the group's research on the role of Gas6/TAM signalling within the TME regarding the pathogenesis of acute leukaemia. In in-vivo experiments of our research group it has been consistently observed that the use of Nilotinib enhances the anti-leukaemic immunity mediated by a deletion of Gas6. Against the background of increasing importance of chemotherapeutic agents as potent modulators of a dysregulated TME, it was hypothesized that Nilotinib may synergize with a Gas6-deficient environment by inducing ICD in Ph+ B-ALL cells. In growth inhibition and Annexin V/Propidium iodide cell death assays Nilotinib was shown to induce cell death in concentration-dependent manner that occurs bimodally in terms of cell death modality ranging between apoptosis and necrosis. By ICD marker analysis, comprising flow-cytometric detection of CALR exposure, chemoluminescence-based ATP measurement and immunoblotting for HMGB1, it was found that Nilotinib-induced cell death is not accompanied by CALR exposure and ATP secretion, but is associated with the release of HMGB1. In macrophages co-culture experiments with Nilotinib-treated leukaemic cells, no relevant shift in terms of macrophages activation and polarisation was observed in either a juxtacrine or paracrine setup. In consistency with the results obtained in the in-vitro experiments, Nilotinib was not potent to elicit a protective immune response in mice within a vaccination assay. Conclusively, Nilotinib was identified to not qualify as bona fide ICD inducer. The role of Nilotinib-induced cell death and HMGB1 release are proposed as objective for further investigation concerning the synergistic interplay between Nilotinib and a Gas6-deficient environment. Efforts addressing exploration and optimisation of the immunological potential of chemotherapeutic agents are a promising approach aimed at providing cancer patients with the best possible treatment in future.

scholarly journals Improving immunotherapy for high grade glioma

2021 ◽  
Author(s):  
◽  
Martin Kent Hunn
Keyword(s):  
T Cells ◽  
Stem Cell ◽  
T Cell ◽  
Mouse Model ◽  
Mononuclear Cells ◽  
Tumour Cells ◽  
Treatment Modalities ◽  
Full Potential ◽  
Promising Alternative ◽  
Tumour Immunity

<p>Glioblastoma multiforme (GBM) is a malignant primary brain tumour that is almost always fatal. Conventional treatment modalities are limited by toxicity. T cell-based immunotherapy is a promising alternative that has the potential to specifically target tumour cells.  The author of this thesis was a principal investigator for a recently completed Phase I clinical trial in which patients with recurrent GBM were treated with surgery, dendritic cell-based immunotherapy and chemotherapy. In addition to conducting the trial in collaboration with others, the author used peripheral blood mononuclear cells from trial participants to assess anti-tumour immune responses before and after treatment. A broad correlation was observed between clinical outcome and anti-tumour immunity, with sustained progression-free survival occurring in two patients with baseline responses that persisted or increased after treatment. However, the overall clinical benefit was modest. For progress to be made, there is a need to develop a more potent vaccine.  With this in mind, a novel “Glioma-Gal” vaccine was devised and tested in an orthotopic mouse model of glioma, This simple vaccine consisted of irradiated autologous tumour cells pulsed with the glycolipid alpha-galactosylceramide, an immunoadjuvant that induces invariant Natural Killer T cells to licence endogenous dendritic cells. The vaccine was shown to be effective in a therapeutic setting when accompanied by depletion of regulatory T cells. Mechanistically, vaccine efficacy was dependent on CD4 T cells and the mediastinal lymph node was shown to be an important site of T cell priming. It was further shown that components of the immune system necessary for the vaccine to work were present and competent in a cohort of GBM patients.  The final chapters explore the idea of enhancing the therapeutic benefit of this vaccine by targeting certain tumour cell subsets or phenotypes. Cancer stem cells (CSC) are proposed to be a subset of tumour cells with a unique capacity for initiating and maintaining tumours. Eliminating these cells may therefore be both necessary and sufficient to achieve cure. Using the same mouse model, a variety of methods were assessed for their ability to isolate or enrich for a CSC subset. Of these, culture in serum-free medium in the presence of certain growth factors was shown to enrich for a more stem cell-like phenotype. However, a vaccine constructed from these stem cell-like cells was not more effective than the standard vaccine. Next, the author tested the hypothesis that a vaccine manipulated to target chemoresistant cells would be more effective than standard vaccine when used in combination with chemotherapy. However, the modified vaccine showed no advantage over standard vaccine in this model. In the course of these experiments, synergy was observed between the vaccine and the chemotherapy agent doxorubicin. The mechanism responsible for this supra-additive effect remains undetermined but is most likely due to an immunomodulatory effect of low dose doxorubicin.  The Glioma-Gal vaccine design holds promise but more studies are needed to realise the full potential of this approach. The data presented in the thesis did not support targeting CSC or chemoresistant cells as ways of achieving this. In contrast, combining the vaccine with immunomodulation was effective and merits further exploration.</p>

Expression and function of CTLA4 in melanoma.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e20040-e20040 ◽  
Author(s):  
Barbara Seliger ◽  
Michele Maio ◽  
Ornella Cuaia ◽  
Luana Calabro
Keyword(s):  
Cell Proliferation ◽  
T Cell ◽  
Immune Responses ◽  
Cell Lines ◽  
Tumour Cells ◽  
Down Regulation ◽  
Tumour Immunity ◽  
Anchorage Independent Growth ◽  
Cell Responses ◽  
And Function

e20040 Background: The definition of co-inhibitory molecules negatively interfering with immune responses has provided novel targets for therapeutic intervention. These include CTLA4, which directly binds to CD80 and CD86 on T cells leading to a down-regulation of immune responses. Recently, anti-CTLA4 antibodies have been established, which were able to stimulate T cell responses and anti-tumour immunity in vitro and cause objective responses in melanoma patients even months later after clinical progression. Since CTLA4 was found to be expressed on tumour cells, which might explain the distinct anti-tumour immunity of CTLA4 in tumour patients, the aim of this study was determine the expression and function of CTLA4 in 60 human tumour cells of distinct origin. Methods: qPCR, Western blot, cytometry and/or immunohistochemistry was performed to determine the expression of CTLA4. Cell proliferation and anchorage-independent growth of CTLA4+tumor cells was determined by XTT and soft agar colony formation, while CTL-mediated lysis was determined by standard chromium release assay. Results: Expression analysis revealed n extremely heterogeneous and tumour-specific CTLA4 mRNA expression in the tumour cell lines tested with the highest frequency (85 %) and expression levels in melanoma. In contrast, only low constitutive CTLA4 surface expression levels, but high levels of intracellular CTLA4 protein were found. Immunohistochemical analyses with seven distinct anti-CTLA4 antibodies showed a heterogeneous staining pattern in selected melanoma cell lines analysed. In order to understand the molecular mechanisms of CTLA4 expression different CTLA4 expression models were established in melanoma and subjected to functional analysis. High levels of CTLA4 expression caused a down-regulation of their cell proliferation as well as a reduced anchorage independent growth. However, CTLA4 expression did not affect the immunogenicity of tumour cells as determined using co-culture assays of CTLA4+tumour cells with either HLA-matched PBMCs or melanoma antigen-specific CTL. Conclusions: In conclusion, CTLA4 is expressed in melanoma cells and reveals non-immunogenic functions by modulating the growth properties, rather than inhibiting T cell responses.

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