Michael A Morse

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..pylori requires an understanding of the complex interactions that make up mucosal immunity. An effective vaccine strategy against H. pylori has the potential to affect significantly on population health worldwide...

..Vaccines for pancreatic cancer have been challenged by a number of factors, especially the immunosuppressive microenvironment within the tumor that allows for escape from immune surveillance...

..To determine the safety and immunologic and clinical efficacy of a dendritic cell vaccine modified to hyperexpress costimulatory molecules and tumor antigen...

..We will discuss the current state of development of cancer vaccines and the relevance for future clinical use of these agents to treat and prevent cancers...

..As considerable research has focused on therapy of colon cancer with viral vectors, this review will illustrate the major concepts of viral therapy of cancers with examples from studies targeting colorectal carcinoma...

..The immune system is "programmed" to down-regulate immune responses once they have become activated to avoid the development of autoimmune disease...

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..The objective of this retrospective study was to determine the effect of multiagent chemotherapy on long-term survival after resection of CLM...

..Based on these results, we feel clinical studies using this approach to target HER2-overexpressing breast cancer, including trastuzumab- and lapatinib-resistant tumors is warranted...

..To compare a neoadjuvant regimen of cisplatin/5-fluorouracil (5-FU) and concurrent radiation therapy (RT) with paclitaxel-based regimens and RT in the management of operable esophageal (EC)/gastroesophageal junction (GEJ) cancer...

..We proposed to address these concerns by using cancer vaccines to stimulate HER2 intracellular domain (ICD)-specific T cell and antibody responses...

..These data suggest that DC differentiation is negatively associated with VEGF levels and may be one explanation for impaired anticancer immunity, especially in patients with advanced malignancies...

..The objective of this retrospective study was to determine if addition of bevacizumab to iri/oxal preoperative chemotherapy increases morbidity after hepatic resection...

..This study was designed to determine the efficacy and tolerability of a novel 2-week regimen of capecitabine, oxaliplatin (OHP), and bevacizumab in patients with chemo-naive advanced colorectal cancer...

..However, prospective randomized trials are needed to determine the optimal timing of chemotherapy...

..We initiated two phase I trials assessing the combination of gefitinib, capecitabine, and radiation in patients with localized pancreatic and rectal cancer...

..To report patterns of disease recurrence after resection of adenocarcinoma of the duodenum and compare outcomes between patients undergoing surgery only vs. surgery with concurrent chemotherapy and radiation therapy (CT-RT)...

..A Phase I trial was undertaken to evaluate the combination of bevacizumab, capecitabine, oxaliplatin, and radiation therapy in patients with rectal cancer...

..To clarify the role of radiotherapy with chemotherapy, we performed a retrospective analysis of resected patients who had undergone chemoradiotherapy...

..These assays will better define the quantity and quality of protective immune responses to viral disease and offer insight into the requirements for protective anti-cancer immunity...

..We addressed the safety of oral eniluracil/5-FU combined with radiation therapy and determined the profile of dose-limiting toxicities and recommended Phase II dose (RPTD) in patients with pancreatic and hepatobiliary cancers...

..This study was designed to determine the efficacy and tolerability of capecitabine, oxaliplatin and bevacizumab in combination with cetuximab as first-line therapy for advanced colorectal cancer...

..We describe the scheme that we are currently using to generate peptide-loaded dendritic cells for our clinical trials of cancer immunotherapy...

..Extrahepatic cholangiocarcinoma is an uncommon but lethal malignancy. We analyzed the role of definitive chemoradiotherapy for patients with nonmetastatic, locally advanced extrahepatic cholangiocarcinoma treated at a single institution...

..The optimal combination of chemotherapeutic agents with RT is undefined. We evaluated a combination of capecitabine, carboplatin, and paclitaxel with RT in a phase I study...

..14). Thus, NK responses following DC vaccination may correlate more closely with clinical outcome than do T cell responses. Monitoring of NK response during vaccine studies should be routinely performed...

..This response may play a critical role in a HIFU-elicited anti-tumor immune response which can be harnessed for more effective treatment...

..To better define the role of adjuvant radiation therapy and chemotherapy, a retrospective analysis of the outcome of patients undergoing surgery and adjuvant therapy was undertaken...

..The aim of this study was to determine the maximally tolerated dose, recommended phase II dose and toxicity profile of capecitabine plus imatinib mesylate combination...

..We conclude that it is feasible and safe to administer mRNA-loaded DC to patients with advanced malignancies...

..This targeting exosome process could also be adapted for the development of more potent vaccines in some viral and parasitic diseases where the classical vaccine approach has demonstrated limitations...

..A phase I study of bevacizumab plus everolimus demonstrated that the combination is safe; activity was seen in several patients with refractory mCRC...

..DC-based immunotherapy in this setting is safe and feasible and may lead to prolonged survival...

..This study evaluated the safety, tolerability, and pharmacokinetics of bevacizumab, everolimus, and erlotinib combination...

..In addition, issues regarding the optimal dose and clinical setting for the application of DC vaccines remain to be resolved, and recent clinical studies have been designed to begin to address these questions...

..We designed and tested several HER2 vaccines devoid of oncogenic activity to develop a safe vaccine for clinical use...

..Characterization of the tumor cells that survive neoadjuvant CRT may help us to identify new or more appropriate targets for systemic therapy...

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..Several strategies tested so far have yielded incomplete, yet promising, results...

..The magnitude of the immune responses generated is fairly modest, and more potent DC loading and maturation strategies will be necessary to optimize these vaccines...

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..To determine the maximally tolerated dose (MTD), recommended phase II dose (RPTD) and toxicity profile of gemcitabine plus irinotecan combination...

..These data suggest that VRP-based vectors can overcome the presence of neutralizing antibodies to break tolerance to self antigen and may be clinically useful for immunotherapy in the setting of tumor-induced immunosuppression...

..Conversely, the use of NKT cells along with anti-Th2 cytokine-neutralizing antibodies or CD4-negative NKT cell subset could enhance the generation of antigen-specific CTLs for adoptive immunotherapy...

..The potency in APC activation produced by mechanical lysis is much stronger than thermal necrosis of the tumor cells. These findings suggest that optimization of treatment strategy may help to enhance HIFU-elicited anti-tumor immunity...

..Advances in miniaturization and automation may also permit characterization of the immune response more rapidly and from smaller amounts of biological material than is possible with existing assay systems...

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..Our findings support clinical explorations to reposition niclosamide for the treatment of CRC...

..Further, we will discuss new strategies to augment the clinical efficacy of cancer vaccines by enhancing vaccine immunogenicity and reversing the immunosuppressive tumor microenvironment...

..We suggest that the HER2-IL-6-STAT3 signaling axis we have defined in breast cancer could prompt new therapeutic or prevention strategies for treatment of HER2-amplified cancers...

..The ability to generate phenotypically mature, IL-12-producing DC1 from peripheral blood mononuclear cells mobilized by Flt3L will have important implications for the development of effective cancer immunotherapy strategies...

..This review highlights the principles underlying virus-based therapies for cancer, with an emphasis on recent developments from the clinic...

..Two patients had partial response; seven patients had stable disease at least 6 months. Oral lonafarnib at 150 mg a.m./100 mg p.m. plus gemcitabine at 1,000 mg/m(2) is the maximum tolerated dose with acceptable safety and tolerability...

..It should be the goal and expectation that this rational approach to immune monitoring will allow the critical appraisal of the most promising vaccine candidates in the context of pivotal, multi-center trials...

..We wished to test whether targeted delivery of an otherwise poorly immunogenic, soluble antigen to APC through their mannose receptors (MR) would induce clinically relevant immunity...

..We also evaluated the extent to which these measures are ready to be implemented in clinical practice, and identified areas for future research...

..One patient had a pathologic complete response. CONCLUSION: Preoperative chemoradiotherapy with oral eniluracil and 5-FU is feasible and well tolerated. Additional investigation is warranted...

..This article will discuss the therapeutic implications of these molecular changes associated with bronchogenic carcinomas and will then review the status of gene therapies for treatment of lung cancer...

..Clinical responses such as stability of disease and tumor regressions have been reported in some patients, particularly with melanoma, myeloma, and prostate cancer...

..Because peptide-based vaccines are human leukocyte antigen-restricted, other more broadly applicable strategies are now being developed to activate WT1-specific immune responses, including the use of WT1-specific viral vectors...

..One hypothesis is that depleting these CD4+CD25+ counter-regulatory T cells in humans with cancer will enhance the efficacy of anticancer immunisations...

..These data have identified a novel functional link between ErbB2 signaling and antiapoptotic pathway mediated by XIAP. Blockade of the IAP antiapoptotic pathway alone or in combination would be an attractive strategy in IBC therapy...

..As such, more preclinical and clinical trials are needed to explore the synergistic effects of chemotherapy combined with immunotherapy, particularly the proper dose and timing of chemotherapy...

..The emphasis of dendritic cell immunotherapy research is increasingly shifting toward the development of strategies to increase the potency of dendritic cell vaccine preparations...

..Genetic modification can be effected by either DNA or RNA, and the genetic material may be delivered by vectors or by physical means. These approaches are now entering human clinical trials...

..Therefore, the authors conducted a systematic review of the literature to determine the available QMs for adjuvant CT and RT in patients with CRC and rated their usefulness for assessing the delivery of quality care...

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..In addition to work being done to develop the most potent effector, other studies are working on improving T-cell trafficking to tumours and interfering with the tumour-induced immunosuppression that can impair in vivo T-cell activity...

..An ongoing Phase II trial evaluates CDX-1307 in patients with newly diagnosed, resectable, hCG-?-expressing bladder cancer, where low tumor burden and early intervention may provide greater potential for benefit...

..TACE may reduce the risk of hemorrhage after cryosurgery but can increase the risk of hepatic failure in patients with poor hepatic function...

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..These data support the further development of such vaccines, and provide guidance for the development of improved agents and protocols for the use of therapeutic vaccination to treat cancer...

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..Wilm's Tumor gene (WT1) is a robust TAA which is overexpressed in many malignancies and has been recently used to develop a novel recombinant adenovirus (Ad-WT1) for antitumor immunotherapy...

..Phase I and II trials have tested this drug in several hematopoietic and solid tumors. Pfizer has initiated Phase III trials to test PF-3512676 in combination with standard chemotherapy for non-small-cell lung cancer...

..To report the successful desensitization of a patient to oxaliplatin utilizing an 8-hour desensitization regimen in a controlled environment...

..This multi-institutional retrospective study compared postoperative outcomes after simultaneous and staged colorectal and hepatic resections...

..Although established for metastatic colorectal (CR) and neuroendocrine (NE) malignancies, the role of partial hepatectomy in management of metastases from other primaries (NCRNE) is not well-defined...

..In this article, the authors will review studies focusing on NK-DC interactions and highlight the most recent clinical findings relating to the potential role of NK cells in DC-based vaccine therapy...

..No viable tumor was identified in the explanted liver. This case establishes that long-term complications associated with PSC and biliary-enteric surgery such as CCA may become apparent in new grafts post-transplant...

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..The therapy is currently undergoing phase I/II clinical trials...

..This strategy appears particularly promising in patients with large HCC. This approach should be investigated further...

..CONCLUSIONS: DCs transfected with total tumor RNA may represent a method for inducing immune responses against the entire repertoire of tumor antigens of surgically resected malignancies...

..A concern for peritoneal seeding of pancreatic cancer via percutaneous FNA is warranted. EUS-guided FNA is recommended as the method of choice for diagnosis in patients with potentially resectable pancreatic cancer...

..This fact, in light of the potential toxicity, would argue for a larger confirmatory trial of HAI in the adjuvant setting, incorporating recent advances in systemic therapy and careful attention to hepatotoxicity...

..Therapies intended to inhibit VEGF or VEGF receptors have demonstrated improved anti-tumor immunity and enhanced responses to cancer vaccines...

..This article reviews preclinical development and data generated from Phase I, II and III studies with regard to the end points reported and immune-related adverse events...

..The future success of clinical trials will depend on the optimization and standardizing of procedures for DC generation, loading, and administration...

..Here we assess the levels of intra-assay, inter-assay, and inter-operator precision, as well as linearity, of CD8+ T cell IFNgamma-based ELISPOT and cytokine flow cytometry (CFC), as well as tetramer assays...

..In this study, we compared the performance of these assays on leukapheresed PBMC shipped overnight in medium versus cryopreserved PBMC from matched donors...

..DMC composition and functions should be standardized and regulations should be harmonized nationally and internationally. Finally, there should be a concerted effort to study the efficacy of various components of the system...