<i>Onco</i>: A Promising Player Amidst Oncology Journals

As the new Editor-in-Chief of the journal, I believe that I must continue the efforts of my predecessor even more actively and with greater enthusiasm and dedication so that the journal becomes a pole of attraction for the publication of excellent studies of basic, translational and clinical research for the treatment of cancer [...

Immune Checkpoint Inhibitors in Cancer Therapy&mdash;How Can We Improve Clinical Benefits?

Immune checkpoint inhibitors (ICIs) are in the spotlight of cancer treatment by increasing the probability for long-term survival in patients with metastatic disease and by considerably prolonging progression-free survival in patients at early disease stages [...

Exploring Essential Issues for Improving Therapeutic Cancer Vaccine Trial Design

Therapeutic cancer vaccines have been at the forefront of cancer immunotherapy for more than 20 years, with promising results in phase I and&mdash;in some cases&mdash;phase II clinical trials, but with failures in large phase III studies. After dozens of clinical studies, only Dendreon&rsquo;s dendritic cell vaccine Sipuleucel-T has succeeded in receiving US FDA approval for the treatment of metastatic castrate-resistant prostate cancer. Although scientists working on cancer immunotherapy feel that this is an essential breakthrough for the field, they still expect that new vaccine regimens will yield better clinical benefits compared to the four months prolonged median overall survival (OS) Sipuleucel-T demonstrated in the IMPACT phase III clinical trial. Clinical development of cancer vaccines has been unsuccessful due to failures either in randomized phase II or&mdash;even worse&mdash;phase III trials. Thus, rigorous re-evaluation of these trials is urgently required in order to redefine aspects and optimize the benefits offered by therapeutic cancer vaccines. The scope of this review is to provide to the reader our thoughts on the key challenges in maximizing the therapeutic potentials of cancer vaccines, with a special focus on issues that touch upon clinical trial design

Cancer Dormancy: A Regulatory Role for Endogenous Immunity in Establishing and Maintaining the Tumor Dormant State

The significant contribution of host immunity in early tumorigenesis has been recently recognized as a result of our better understanding of the molecular pathways regulating tumor cell biology and tumor-lymphocyte interactions. Emerging evidence suggests that disseminated dormant tumor cells derived from primary tumors before or after immune surveillance, are responsible for subsequent metastases. Recent trends from the field of onco-immunology suggest that efficiently stimulating endogenous anticancer immunity is a prerequisite for the successful outcome of conventional cancer therapies. Harnessing the immune system to achieve clinical efficacy is realistic in the context of conventional therapies resulting in immunogenic cell death and/or immunostimulatory side effects. Targeted therapies designed to target oncogenic pathways in tumor cells can also positively regulate the endogenous immune response and tumor microenvironment. Identification of T cell inhibitory signals has prompted the development of immune checkpoint inhibitors, which specifically hinder immune effector inhibition, reinvigorating and potentially expanding the preexisting anticancer immune response. This anticancer immunity can be amplified in the setting of immunotherapies, mostly in the form of vaccines, which boost naturally occurring T cell clones specifically recognizing tumor antigens. Thus, a promising anticancer therapy will aim to activate patients’ naturally occurring anticancer immunity either to eliminate residual tumor cells or to prolong dormancy in disseminated tumor cells. Such an endogenous anticancer immunity plays a significant role for controlling the balance between dormant tumor cells and tumor escape, and restraining metastases. In this review, we mean to suggest that anticancer therapies aiming to stimulate the endogenous antitumor responses provide the concept of the therapeutic management of cancer

Immunobiology of HER-2/neu oncoprotein and its potential application in cancer immunotherapy.

HER-2/neu (also known as HER2 or c-erb-B2) is a 185-kDa protein receptor with tyrosine kinase activity and extensive homology to the epidermal growth factor (EGF) receptor. HER-2/neu is expressed in many epithelial tumors and known to be overexpressed in approximately 20-25% of all ovarian and breast cancers, 35-45% of all pancreatic adenocarcinomas, and up to 90% of colorectal carcinomas. HER-2/neu overexpression represents a marker of poor prognosis. HER-2/neu-positive tumor cells are potentially good targets for tumor-reactive cytotoxic T lymphocytes which have been utilized in immunotherapeutic trials. In addition, the "humanized" monoclonal antibody Herceptin has been tested in several clinical trials and proved to be an effective adjuvant therapy for HER-2/neu-positive breast and ovarian cancers. Vaccinations aiming at generating T-cell responses are being examined in both experimental and clinical trials. Natural immunity at the level of T and B cells has been observed in patients with HER-2/neu-positive tumors confirming the immunogenicity of HER-2/neu and encouraging vaccination trials with HER-2 protein-derived subunits or synthetic peptides. This review summarizes recent data from patients with various types of HER-2/neu-overexpressing cancers carrying different HLA alleles and exhibiting preexistent immunity to HER-2/neu-derived synthetic peptides. It also discusses potential advantages of the various vaccination approaches to immunotherapy targeting the HER-2/neu molecule.Journal ArticleReviewinfo:eu-repo/semantics/publishe

The mannosylated extracellular domain of Her2/neu produced in <it>P. pastoris </it>induces protective antitumor immunity

Abstract Background Her2/neu is overexpressed in various human cancers of epithelial origin and is associated with increased metastatic potential and poor prognosis. Several attempts have been made using the extracellular domain of Her2/neu (ECD/Her2) as a prophylactic vaccine in mice with no success in tumor prevention. Methods The extracellular domain of Her2/neu (ECD/Her2) was expressed in yeast P. pastoris, in a soluble highly mannosylated form. The immune response of the immunization with this recombinant ECD/Her2 was analyzed using immunoprecipitation and western blot analysis, proliferation and cytotoxicity assays as well as specific tumor growth assays. Results Mannosylated ECD/Her2 elicited a humoral response with HER2/neu specific antibodies in vaccinated mice, which were able to reduce the proliferation rate of cancer cells in vitro. Moreover, it elicited a cellular response with Her2/neu-specific CTL capable of lysing tumor cells, in vitro. When immunized Balb/c and HHD mice were challenged with Her2/neu-overexpressing cells, tumor growth was inhibited. Conclusion Here we report on the efficacy of the extracellular domain of human Her2/neu produced in yeast P. pastoris, which confers mannosylation of the protein, to act as a potent anti-tumor vaccine against Her2/neu overexpressing tumors. Specific cellular and humoral responses were observed as well as efficacy.</p

Reinstating endogenous antitumor immunity: The concept of therapeutic management of cancer

Strong evidence points to the role of cancer immunoediting and tumor immune infiltrates in regulating cancer progression. By understanding the immune tumor microenvironment, we can now target key pathways that suppress endogenous antitumor responses, thereby re-instating such immune responses and identifying novel targets for immune therapies. Therapies targeting oncogenic pathways and checkpoint blockades turn on a new paradigm shift in immune-therapy for cancer with remarkable clinical efficacy seen in various malignancies. However, a lot of cancer patients will fail to respond and therefore, it becomes crucial to identify biomarkers to predict who of the patients will most likely benefit from these therapies

Cell culture medium composition and translational adult bone marrow-derived stem cell research.

The use of fetal calf serum (FCS) for the culture of cells to be used in clinical trials raises potential hazards that cannot be neglected, but this is a regulatory issue. However, as specifically regards the isolation and expansion of human mesenchymal stem cells (MSCs), unfortunately serum-free media have not yet been defined. The alternative of using autologous serum is feasible only for the minority of clinical protocols involving low numbers of MSCs, because a minimum concentration of 10% in the culture medium is required. Besides, because allogeneic serum results in MSC growth arrest and death, use of pooled human serum does not represent an alternative. Finally, vast numbers of MSCs cultured in FCS-containing media have already been used in many clinical trials targeting a variety of disorders, without any significant side effects, including ventricular arrhythmia.LetterFLWINinfo:eu-repo/semantics/publishe