Overview of Tumor Cell–Based Vaccines

Copier, John; Dalgleish, Angus

doi:10.1080/08830180600992472

Cited by 103 publications

(72 citation statements)

References 108 publications

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“…The experiments in which PDT vaccine cells were exposed to annexin V and apoptosis inhibitor Z-DEVD (Figures 4 and 5) demonstrate that cell death process and its markers on the cell surface (such as phosphatidylserine) are critical for effective immune processing of these cells. Cell death manipulation is a recognised strategy for augmenting the efficacy of whole-cell cancer vaccines (Copier and Dalgleish, 2006). Our recent findings suggest that the gene encoding serum amyloid P component (SAP), pentraxin protein involved in the disposal of dead cells, is upregulated in the liver and tumour of PDT vaccine treated mice (J Sun and M Korbelik, unpublished results).…”

Section: Discussionmentioning

confidence: 99%

“…The polyvalent vaccines, such as autologous whole-cell vaccines represented by PDT vaccines, secure greater coverage of potential/diverse tumour antigens (even if most of them are unknown) and include the necessary determinants for helper T cells (Copier and Dalgleish, 2006;Emens, 2006). Autologous whole-cell vaccines are optimally conditioned to express antigens in patient-matched MHC and are less likely to encounter 'tumour escape' by downregulation of antigen expression (Khong and Restifo, 2002;Emens, 2006).…”

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confidence: 99%

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Photodynamic therapy-generated vaccines: relevance of tumour cell death expression

2007

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Recent investigations have established that tumour cells treated in vitro by photodynamic therapy (PDT) can be used for generating potent vaccines against cancers of the same origin. In the present study, cancer vaccines were prepared by treating mouse SCCVII squamous cell carcinoma cells with photosensitiser chlorin e6-based PDT and used against poorly immunogenic SCCVII tumours growing in syngeneic immunocompetent mice. The vaccine potency increased when cells were post-incubated in culture after PDT treatment for 16 h before they were injected into tumour-bearing mice. Interfering with surface expression of phosphatidylserine (annexin V treatment) and apoptosis (caspase inhibitor treatment) demonstrated that this post-incubation effect is affiliated with the expression of changes associated with vaccine cell death. The cured mice acquired resistance to re-challenge with the same tumour, while the engagement of cytotoxic T lymphocytes was demonstrated by detection of high numbers of degranulating CD8 þ cells in vaccinated tumours. The vaccines prepared from ex vivo PDT-treated SCCVII tumour tissue were also highly effective, implying that surgically removed tumour tissue can be directly used for PDT vaccines. This opens attractive prospects for employing PDT vaccines tailored for individual patients targeting specific antigens of the patient's tumour.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Photodynamic therapy-generated vaccines: relevance of tumour cell death expression

2007

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“…Enhancing the body's natural ability to trigger the immune system to kill cancer cells underlies the principle of biological therapies. These can take the form of interferons (IFNs) and growth factors, as well as a DC-vaccine approach (Dalgleish, 2004;Copier and Dalgleish, 2006), which are administered as an attempt to stimulate or restore the ability of the immune system to fight disease (Weiner et al, 2009). Recently, chemotherapeutic agents have been added to the list of biological response modifiers.…”

Section: Discussionmentioning

confidence: 99%

Pre-treatment with chemotherapy can enhance the antigenicity and immunogenicity of tumours by promoting adaptive immune responses

et al. 2009

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Background: Some cancer patients are immuno-compromised, and it has been long felt that immune-intervention is not compatible with standard chemotherapies. However, increasing evidence suggests that standard chemotherapy drugs may stimulate beneficial changes in both the immune system and tumour. Methods: We have assessed the expression of human leucocyte antigen class 1 (HLA1) on tumour cells before and after chemotherapy agents (cyclophosphamide, oxaliplatin or gemcitabine). In addition, we show that chemotherapy-stressed tumour cells may release cytokines that enhance the interactions between dendritic cells (DCs) and T cells into growth media. Results: Here we report that some chemotherapy agents can increase HLA1 expression in tumour cells, even when expression is low. Increases were associated with killing by cytotoxic T cells, which were negated by HLA1-blockade. Furthermore, T-cell function, as indicated by increased proliferation, was enhanced as supernatants derived from tumours treated with chemotherapy augmented DC-maturation and function. Conclusion: There is evidence that a facet of immune surveillance can be restored by appropriate chemotherapy agents. Also, tumours exposed to some chemotherapy may secrete cytokines that can mature DCs, which ultimately enhances T-cell responses.

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“…Furthermore, the immunogenicity of whole tumor-cell vaccines can be augmented by modifying tumor cells with expression of GM-CSF or other immunostimulatory genes to generate improved antitumor T-cell immunity. To date, autologous and allogeneic whole tumor-cell-based vaccines have been intensely studied in clinical trials in patients with melanoma, renal cell and hepatocellular carcinomas, lung, prostate, breast, colorectal, cervical, pancreatic, or ovarian cancer (1)(2)(3). However, there is evidence that tumor cell-derived cytokines (e.g., VEGF, IL10, and TGFb) and biologic factors (e.g., galectin-1, indoleamine 2,3-dioxygenase, lipid droplets) suppress dendritic cell (DC) maturation and T-cell activation, thus limiting the efficacy and efficiency of whole cell-based vaccination (4,5).…”

Section: Introductionmentioning

confidence: 99%

Cell-free Tumor Microparticle Vaccines Stimulate Dendritic Cells via cGAS/STING Signaling

Zhang

Tang

Zhang

et al. 2015

Cancer Immunology Research

121

149

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Tumor antigens and innate signals are vital considerations in developing new therapeutic or prophylactic antitumor vaccines. The role or requirement of intact tumor cells in the development of an effective tumor vaccine remains incompletely understood. This study reveals the mechanism by which tumor cell-derived microparticles (T-MP) can act as a cell-free tumor vaccine. Vaccinations with T-MPs give rise to prophylactic effects against the challenge of various tumor cell types, while T-MP-loaded dendritic cells (DC) also exhibit therapeutic effects in various tumor models. Such antitumor effects of T-MPs are perhaps attributable to their ability to generate immune signaling and to represent tumor antigens. Mechanically, T-MPs effectively transfer DNA fragments to DCs, leading to type I IFN production through the cGAS/STING-mediated DNA-sensing pathway. In turn, type I IFN promotes DC maturation and presentation of tumor antigens to T cells for antitumor immunity. These findings highlight a novel tumor cell-free vaccine strategy with potential clinical applications.

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Overview of Tumor Cell–Based Vaccines

Cited by 103 publications

References 108 publications

Photodynamic therapy-generated vaccines: relevance of tumour cell death expression

Photodynamic therapy-generated vaccines: relevance of tumour cell death expression

Pre-treatment with chemotherapy can enhance the antigenicity and immunogenicity of tumours by promoting adaptive immune responses

Cell-free Tumor Microparticle Vaccines Stimulate Dendritic Cells via cGAS/STING Signaling

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