In Molecular Diagnostics for Melanoma: Methods and Protocols, expert researchers and clinicians in the field of melanoma provide updated information on biomarkers and assays for diagnosis, prognosis, and assays predicting response to treatment for routine testing. The focus of the volume is on biomarkers with established clinical validity rather than those on early discovery stage. With additional in-depth discussion of the molecular biology and pathology of melanoma, treatment options in adjuvant and metastatic setting, and implications of biomarker testing for clinical management of melanoma patients. Written in the highly successful Methods in Molecular Biology series format, chapters include extensive introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and key tips on troubleshooting and avoiding known pitfalls. Comprehensive and practical, Molecular Diagnostics for Melanoma: Methods and Protocols seeks to provide both clinicians and scientists with technical information and extensive background information on the wide ranging approaches available in the field of diagnostics of melanoma.

This book discusses the mechanisms leading to immune-mediated tissue rejection following the hypothesis that independent of the disease process the final effector mechanism is shared by most (but not all) pathologies and it is relatively simple. The book covers evidence gathered to support the thesis by studies performed in humans during rejection or in experimental models and will focus particularly (but not exclusively) on the analysis of the rejected tissue rather than the systemic circulation. Several disease processes are discussed including example of chronic inflammatory process without resolution of the pathologic process and acute one with resolution of the pathologic process (clearance of pathogen, rejection of tumor) or unwanted tissue destruction (allograft rejection, autoimmunity).

Active specific immunotherapy is a promising but investigational modality in the management of cancer patients. Currently, several different cancer vaccine formulations such as peptides, proteins, antigen-pulsed dendritic cells, whole tumor cells, etc. in combination with various adjuvants and carriers are being evaluated in clinical trials (1-3). To determine the optimal cancer vaccine strategy, a surrogate immunological end-point that correlates with clinical outcome needs to be defined, since it would facilitate the rapid comparison of these various formulations. Traditional immunological assays such as ELISA, proliferation and cytotoxicity assays can detect immune responses in vaccinated patients but are not quantitative. In contrast, novel assays such as enzyme-linked immunospot (ELISPOT) assay, intracellular cytokine assay and tetramer assay can quantitate the frequency of antigen-specific T cells. Of these, the ELISPOT assay has the 5 lowest detection limit with 1/10 peripheral blood mononuclear cells (PBMC) and has been determined to be one of the most useful assays to evaluate immune response to cancer vaccines (4). However, the IFN-? ELISPOT assay is not an exclusive measure of cytotoxic T-lymphocyte (CTL) activity as non-cytotoxic cells can also secrete IFN-?. Additionally, CTL with lytic activity do not always secrete IFN-? (5). A more relevant approach to assess functional activity of cytotoxic lymphocytes would be to measure the secretion of molecules that are associated with lytic activity. One of the major mechanisms of cell-mediated cytotoxicity involves exocytosis of cytoplasmic granules from the effector toward the target cell.

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 from the laboratory trial to the bedside for the practicing oncologist. Cancer Vaccines: From Research to Clinical Practice: Analyzes the most promising classes of investigational immunotherapies, integrating their scientific rationale and clinical potential Discusses "theranostics" as pertaining to immunotherapy, i.e., using molecular diagnostics to identify patients that would most likely benefit from a therapy Presents the new paradigm of biomarker guided R&D and clinical development in immunotherapy of cancer Reviews bottlenecks in translational process of immunotherapies and offers strategies to resolve them

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: Challenges and Opportunities in Translation is the first text in the field to bring immunotherapy treatments from the laboratory trial to the bedside for the practicing oncologist. Cancer Vaccines: Challenges and Opportunities in Translation: * Critically analyzes the most promising classes of investigational immunotherapies, integrating their scientific rationale and clinical potential * Discusses "theranostics" as pertaining to immunotherapy, i.e., using molecular diagnostics to identify patients that would most likely benefit from a therapy * Presents the new paradigm of biomarker guided R&D and clinical development in immunotherapy of cancer * Reviews bottlenecks in translational process of immunotherapies and offers strategies to resolve them

In Molecular Diagnostics for Melanoma: Methods and Protocols, expert researchers and clinicians in the field of melanoma provide updated information on biomarkers and assays for diagnosis, prognosis, and assays predicting response to treatment for routine testing. The focus of the volume is on biomarkers with established clinical validity rather than those on early discovery stage. With additional in-depth discussion of the molecular biology and pathology of melanoma, treatment options in adjuvant and metastatic setting, and implications of biomarker testing for clinical management of melanoma patients. Written in the highly successful Methods in Molecular Biology series format, chapters include extensive introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and key tips on troubleshooting and avoiding known pitfalls. Comprehensive and practical, Molecular Diagnostics for Melanoma: Methods and Protocols seeks to provide both clinicians and scientists with technical information and extensive background information on the wide ranging approaches available in the field of diagnostics of melanoma.

This book discusses the mechanisms leading to immune-mediated tissue rejection following the hypothesis that independent of the disease process the final effector mechanism is shared by most (but not all) pathologies and it is relatively simple. The book covers evidence gathered to support the thesis by studies performed in humans during rejection or in experimental models and will focus particularly (but not exclusively) on the analysis of the rejected tissue rather than the systemic circulation. Several disease processes are discussed including example of chronic inflammatory process without resolution of the pathologic process and acute one with resolution of the pathologic process (clearance of pathogen, rejection of tumor) or unwanted tissue destruction (allograft rejection, autoimmunity).

Active specific immunotherapy is a promising but investigational modality in the management of cancer patients. Currently, several different cancer vaccine formulations such as peptides, proteins, antigen-pulsed dendritic cells, whole tumor cells, etc. in combination with various adjuvants and carriers are being evaluated in clinical trials (1-3). To determine the optimal cancer vaccine strategy, a surrogate immunological end-point that correlates with clinical outcome needs to be defined, since it would facilitate the rapid comparison of these various formulations. Traditional immunological assays such as ELISA, proliferation and cytotoxicity assays can detect immune responses in vaccinated patients but are not quantitative. In contrast, novel assays such as enzyme-linked immunospot (ELISPOT) assay, intracellular cytokine assay and tetramer assay can quantitate the frequency of antigen-specific T cells. Of these, the ELISPOT assay has the 5 lowest detection limit with 1/10 peripheral blood mononuclear cells (PBMC) and has been determined to be one of the most useful assays to evaluate immune response to cancer vaccines (4). However, the IFN-? ELISPOT assay is not an exclusive measure of cytotoxic T-lymphocyte (CTL) activity as non-cytotoxic cells can also secrete IFN-?. Additionally, CTL with lytic activity do not always secrete IFN-? (5). A more relevant approach to assess functional activity of cytotoxic lymphocytes would be to measure the secretion of molecules that are associated with lytic activity. One of the major mechanisms of cell-mediated cytotoxicity involves exocytosis of cytoplasmic granules from the effector toward the target cell.

Despite advancements in the cloning of the total human genome, biomedical innovations at the patient level are becoming rare events. However, translational medicine is a burgeoning science that shows the potential to reverse the trend. This textbook will comprise a state-of-the-art survey of translational medicine, with emphasis on its emerging scientific backbone, its strengths, and its weaknesses. It explores all aspects of preclinical and clinical issues that are relevant to the success of translational pharmaceutical or medical device or diagnostic innovations, including target risk assessment, biomarker evaluation, and predictivity grading for both efficacy and toxicity; early human trial designs that are adequate to guide stop or go decisions on the grounds of biomarker panels; and biostatistical methods to analyze multiple readout situations and quantify risk projections. The book provides guidance to design smart profiling strategies for new approaches aimed at cutting timelines and concentrating on the comparison of quality issues of early developmental processes for pharmaceutical and biotechnology research. By furthering the substantiation of translational medicine, creating awareness about its potential to promote innovations into clinical practice, and examining the terminology surrounding current biotechnologies, this book hopes to create a dialogue about translational science and what this will mean for patient care in the near future.

This book addresses the biological processes relevant to the immune phenotypes of cancer and their significance for immune responsiveness, based on the premise that malignant cells manipulate their surroundings through an evolutionary process that is controlled by interactions with innate immune sensors as well as the adaptive recognition of self/non-self. Checkpoint inhibitor therapy is now an accepted new form of cancer treatment. Other immuno-oncology approaches, such as adoptive cell therapy and metabolic inhibitors, have also shown promising results for specific indications. Immune resistance is common, however, limiting the efficacy of immunotherapy in many common cancer types. The reasons for such resistance are diverse and peculiar to the immune landscapes of individual cancers, and to the treatment modality used. Accordingly, approaches to circumvent resistance need to take into account context-specific genetic, biological and environmental factors that may affect the cancer immune cycle, and which can best be understood by studying the target tissue and correlated systemic immune markers. Understanding the major requirements for the evolutionary process governing human cancer growth in the immune-competent host will guide effective therapeutic choices that are tailored to the biology of individual cancers.

Interleukin-10 (IL-10) is regarded as an immune suppressant cytokine. This reputation is due to the experimental observation that IL-10 decreases the function of antigen presenting cells and T helper 1 type immune responses. Surprisingly, however, IL-10 has potent anti-cancer effects since most experimental models demonstrate immune-mediated anti-tumor effects whether IL-10 is locally (tumor transfectant models) or systemically (transgenic models, administration of soluble cytokine) provided. In addition, recent work has suggested that polymorphisms of the promoter region of IL-10 may segregate propulsions in high and low producers. Surprisingly, high IL-10 producers may be more predisposed to acquire cancer and other diseases. Finally, human observations demonstrate that systemic administration of IL-10 to normal volunteers is associated with very little toxicity and pro-inflammatory properties mediated through activation of effector cells of the innate immune response. Thus, the role that interleukin-10 plays in vivo in physiological or pathological conditions remains controversial. Thus, there exists a compelling need to summarize in a book the state of the science of this important cytokine. With the assistance of several experts in this field, Interleukin-10 has attempted this endeavor.