A recent advance in anti-cancer therapies has been the use of cancer cells to develop vaccines. However, immunization with cancer cell-based vaccines has not resulted in significant long-term therapeutic benefits. A possible reason for this is that while cancer cells provide surface antigens that are targets for a desired immune response, they also contain a high abundance of housekeeping proteins, carbohydrates, nucleic acids, lipids, and other intracellular contents that are ubiquitous in all mammalian cells. These ubiquitous molecules are not the intended targets of this therapy approach, and thus, the immune response generated is not sufficient to eliminate the cancer cells present. In this review, a discussion of the cell surface of cancer cells is presented in relation to the goals of improving antigen composition of cancer cell-based vaccines. Strategies to enrich vaccines for cancer-specific antigens are also discussed.
The optimization of drug therapy according to the personal characteristics of patients is a perspective direction in modern medicine. One of the possible ways to achieve such personalization is through the application of “omics” technologies, including current, promising metabolomics methods. This review demonstrates that the analysis of pre-dose metabolite biofluid profiles allows clinicians to predict the effectiveness of a selected drug treatment for a given individual. In the review, it is also shown that the monitoring of post-dose metabolite profiles could allow clinicians to evaluate drug efficiency, the reaction of the host to the treatment, and the outcome of the therapy. A comparative description of pharmacotherapy personalization (pharmacogenomics, pharmacoproteomics, and therapeutic drug monitoring) and personalization based on the analysis of metabolite profiles for biofluids (pharmacometabolomics) is also provided.
Immune-mediated damage to tumor vessels is a potential means of preventing solid tumor progression. Antiangiogenic cancer vaccines capable of inducing this kind of damage include formulations comprised of endothelial cell-specific antigens. Identification of antigens capable of eliciting efficient vaccination is difficult because the endothelial cell phenotype is affected by surrounding tissues, including angiogenic stimuli received from surrounding tumor cells. Therefore, phenotype endothelial cell variations (heterogeneity) were examined in the context of the development of an efficient vaccine using mass spectrometry-based cell surface profiling. This approach was applied to primary human microvascular endothelial cell (HMEC) cultures proliferated under growth stimuli provided by either normal tissues (growth supplement from human hypothalamus) or cancer cells (MCF-7, LNCap and HepG2). It was found that tumors induced pronounced, tumor type-dependent changes to HMEC surface targets that in an in vitro model of human antiangiogenic vaccination directly facilitated HMEC escape from cytotoxic T cell-mediated cell death. Furthermore, it was found that tumors influenced the HMEC phenotype unidirectionally and that HMEC imunogenicity was reciprocal to the intensity of tumor-induced changes to the HMEC surface. These findings provide data for the design of tumor-specific endothelial cell based vaccines with sufficient immunogenicity without posing a risk to the elicitation of autoimmunity if administered in vivo.
cross-contamination between cell lines is widely prevalent, and continues to be a major problem [6][7][8][9] . From the existing estimates, it is know that during the cultivation process up to 36% of cell lines have already a different origin from their initial cell lines. 10 From the known cell authentication methods, 11 short tandem repeat profiling (DNA fingerprinting) 10 is considered to be the most powerful method that provides an international reference standard for authentication of human cell lines. 12 However, this method exhibits some limitations: DNA fingerprinting is usually so complex and labor intensive that the cost of fingerprinting can be up to $200 for each cell line, 12 moreover DNA fingerprinting profiles could be very difficult to interpret and store in computer databases. Another major limitation is that the common cell culture protocols may dramatically affect the fingerprinting profile of certain cell lines thus making the definition of their origin improbable 13 . The control of cell propagation by DNA fingerprinting, when following a GTP (Good Tissue Practice) protocol, may increase the cost of end-product substantially.
The comparative proteomic study of cell surfaces of native and drug-treated cancer cells was performed. To this end, cell proteomic footprinting, which reflects the mass spectrometry profiling of cell surface proteins, was applied to breast adenocarcinoma cells (MCF-7), which were untreated or treated with doxorubicin, tamoxifen, or etoposide. The footprints of drug-treated cells were compared with the footprints of untreated cells and the footprint of a randomly selected control cancer cell culture. It was found that drug-treated cells have reproducible, pronounced, and drug-specific changes in cell surface protein expression. Cytotoxicity assays, which are an in vitro model of human antitumor vaccination, revealed that the degree of these changes correlates directly with the ability of the cancer cells to escape cell death induced by a cytotoxic T-cell-mediated immune response. Moreover, cancer cells escape from the immune response was linearly approximated (R2 equal to 0.99) with the degree by which their proteomic footprints diverged from the footprint of the targeted (native) cancer cells. From these findings, it was concluded that the design of anticancer vaccines intended to prevent cancer recurrence after primary treatment should consider the drug-specific changes in cancer cell-surface antigens. Such changes can be easily identified by cell proteomic footprinting, renewing hopes for development of efficient cellular cancer vaccines.
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