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In recent years, there has been a considerable interest in the development of immunotherapeutic approaches for treating cancers, including strategies for inducing antigen-specific cytotoxic T cells (CTLs) capable of killing tumour cells in situ. These approaches include both the active induction of CTLs by vaccination of tumour bearing patients, and the ex vivo expansion of tumour-specific CTLs for adoptive cellular transfer. One promising approach has been through the generation of hybrid cells, formed by fusion of professional antigen presenting cells (pAPCs) with tumour cells expressing relevant tumour associated antigens. Dendritic cells (DCs) represent the most potent form of pAPCs, and have been widely used in the generation of APC/tumour cell hybrid vaccines, in the context of a range of tumour types. Studies of fusion cell vaccines in animals have demonstrated not only the induction of tumour-specific CTLs, but also protection against subsequent tumour challenge and regression of established tumours. Results of clinical trials in patients have been less dramatic, but have shown the ability of hybrid vaccines to induce tumour-specific T cell responses, in some instances associated with disease stabilization or tumour regression. In addition to dendritic cell fusion vaccines, a number of non-DC fusion vaccines have been described.
- Volume is divided into four sections, allowing easy navagation for researchers and practicing physicians - Text includes clinical trials - Written by leaders in the field
The induction of immune responses against tumor cells by vaccination is rapidly evolving as a therapeutic modality with new potentials for the treatment of cancer. It is based on the fact that our immune system can identify tumor cells and, once activated, is capable of developing specific immunity against the neoplastic cells. Numerous observations and intense research clearly document the major contribution of the immune system to the prevention of cancer. And there are many re ports of patients suffering from malignant melanoma or other tumors who mount a spontaneous immune response against their tumor cells that results in tumor regression. Based on the recent advances in our understanding of the compo nents of our immune system, their interactions and the regulation of immune responses, we are now able to design vaccination strategies that induce or enhance cell-mediated immunity against tumors. A ma jor advancement came with the identification and characterization of relevant tumor antigens, which are suitable target structures for anti-tu mor immune response. First clinical trials using such vaccine strategies have yielded encouraging results in patients. However, in spite of many reported cases of successful therapy of cancer by vaccination many patients still do not experience relief after such treatments. These initial clinical trials and the accompanying investigations have revealed a number of important results that indicate the direction of future re search and development in the field.
The most efficient way to mount a sustained immune response is to target antigens to antigen presenting cells that trigger both innate and adaptive immune responses. A comprehensive view of the current approaches to the design of new antigenic formulations will enhance our understanding and perspective of targeted immunotherapy. The aim of this Research Topic is to provide an overview of the currently adopted targeting strategies by a collection of articles on: 1.Novel approaches of antigen targeting for immunotherapeutic strategies against cancer and/or infectious diseases. 2. Diversity and biology of dendritic cell subsets in human and mouse. 3. Combined strategies for the delivery of antigens and adjuvant molecules that stimulate innate immune responses and their influence on the quality of immune responses. 4. Impact of the receptor mediate intracellular trafficking on antigen presentation.
Dendritic cells (DC) are highly potent antigen-presenting cells that are gaining status as a preferred adjuvant for cancer vaccine immunotherapy. DC derive their potency from the expression of MHC class I and MHC class II molecules, costimulatory molecules and adhesion molecules that provide secondary signals for the stimulation of naive T cells, CD4+ T-helper cells, CD8+ cytotoxic T lymphocytes (CTLs), NK and NKT cells (1,2). Because DC have the capacity to take up various types of molecules, the cells can be loaded with tumor-associated antigens (TAAs) in various forms and applied as vaccines. A novel DC-based approach is vaccination with DC-tumor cell hybrids generated by fusion of tumor cells with DC to combine sustained tumor antigen expression with the antigen-presenting and immune stimulatory capacities of DC. In animal models, immunization with DC-tumor cell hybrids can effectively provide anti-tumor protection or eradicate established disease. Hybrids of autologous DC comprised of tumor cell lines or primary human tumor cells (including breast carcinoma cells) have been shown to induce CTL responses against autologous tumor cell types in vitro. Two recent phase I clinical trials for the treatment of renal cell carcinoma and glioma have demonstrated that vaccination with DC-tumor cell hybrids can safely induce anti-tumor immune responses in patients. Traditional fusion technology using polyethylene glycol (PEG) is hampered by a lack of reproducibility and difficulties in method standardization. As an alternative, electrofusion has been used for production of DC-tumor cell hybrids.
Recent advances in immunology and biology have opened new horizons in cancer therapy, included in the expanding array of cancer treatment options, which are immunotherapies, or cancer vaccines, for both solid and blood borne cancers. Cancer Vaccines: From Research to Clinical Practice is the first text in the field to bring immunotherapy treatments
Therapeutic cancer vaccines represent a type of active cancer immunotherapy. Clinicians, scientists, and researchers working on cancer treatment require evidence-based and up-to-date resources relating to therapeutic cancer vaccines. Vaccines for Cancer Immunotherapy provides a reference for cancer treatment for clinicians and presents a well-organized resource for determining high-potential research areas. The book considers that this promising modality can be made more feasible as a treatment for cancer. Chapters cover cancer immunology, general approaches to cancer immunotherapy, vaccines, tumor antigens, the strategy of allogeneic and autologous cancer vaccines, personalized vaccines, whole-tumor antigen vaccines, protein and peptide vaccines, dendritic cell vaccines, genetic vaccines, candidate cancers for vaccination, obstacles to developing therapeutic cancer vaccines, combination therapy, future perspectives and concluding remarks on therapeutic cancer vaccines. - Introduces the feasible immunotherapeutic vaccines for patients with different types of cancer - Presents the status of past and current vaccines for cancer treatment - Considers advantages and disadvantages of different therapeutic cancer vaccines - Looks at the combination of vaccines and other modalities, including immunotherapeutic and conventional methods - Analyzes obstacles to development of therapeutic cancer vaccines - Gives a view on future perspectives in the application of therapeutic cancer vaccines
Harnessing the potential of the human body's own immune system to attack malignant tumor cells has been the goal of many scientific investigators in recent years, with advances in cancer biology and immunology enabling cancer immunotherapy to become a reality. World-class bench and clinical researchers have joined forces to collaborate and review current developments and trends in cancer immunology for the purposes of this book, and the result is a promising review of contemporary clinical treatments. In each chapter the authors present the scientific basis behind such therapeutic approaches, including cancer vaccines with special focus on prostate cancer, melanoma and novel approaches utilizing both innate and adaptive immune responses.
The idea of a preventive vaccine against cancer has been extremely attractive because of the immune system’s ability to develop specific and long-lasting immunological memory. Dendritic cells, which present antigen to T cells, sit at a critical point in the activation of the immune system because they are able to activate both B cells and T cells. The first DC vaccines were tested in humans in 1998. In 2010 the first DC vaccine was FDA approved for treatment of patients with advanced prostate cancer. This vaccine showed a survival advantage of 4.3 months. This vaccine was extremely safe, with low rates of adverse events. In this chapter we discuss the history of DC vaccines, the development of DC vaccines including Sipuleucel-T, and the future directions of DC vaccines. This includes strategies for combining DC vaccines with other therapies, including hormone therapy, additional immunotherapy, and chemotherapy.
Cancer Vaccines and Tumor Immunity offers a review of the basic scientific discoveries that have moved forward into clinical trials. Presented in the context of real-world human research and experimentation, these major scientific advances demonstrate how our understanding of immune activation, T-regulatory cells, and autoimmunity will impact cancer vaccine design. The authors also explain how vaccination in the context of bone marrow transplantation will open new avenues for clinical study in the future.