Ian D Davis

..CONCLUSION: Radioimmunotherapy using 131I-huA33 shows promise in targeting colorectal tumors, and is deliverable at a maximum tolerated dose of 40 mCi/m2. Further studies of 131I-huA33 in combination with chemotherapy are planned...

..In conclusion, repeated intravenous doses of up to 50 mg/m(2) of cG250 are safe. Furthermore cG250 has a long half-life and targets clear cell RCC effectively...

..No antitumour responses were observed. In conclusion, weekly cG250 with daily low-dose subcutaneous IL-2 is well tolerated. IL-2 does not influence cG250 biodistribution or increase HACA...

..Treatments directed at these interactions bring new challenges in terms of how best to develop these strategies, and require approaches that differ in many ways from conventional anticancer therapies...

..MAGE-A10-specific T cells with a skewed T-cell receptor repertoire were detected in 1 patient in blood ex vivo and from tumor biopsies. Vaccination with FLDCs pulsed with peptides is safe and primes immune responses to cancer antigens...

..In an unplanned analysis, vaccinated patients appeared to have superior clinical outcomes to those treated with placebo or protein alone. The vaccine is safe and highly potent immunologically...

..The beginning of the 21st century brings the possibility of a new era of effective cancer immunotherapy, combining rational, immunological treatments with conventional therapies to improve the outcome for patients with cancer...

..Recently conducted phase 1 trials in metastatic melanoma and renal cell carcinoma have shown that recombinant IL-21 has a favorable safety profile and support its continued investigation as a potential anticancer drug...

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..To investigate the pharmacokinetics and tolerability of recombinant human interleukin-4 (rhuIL-4), administered by daily subcutaneous injection, in patients with advanced cancer...

..At the same time, it is possible to recruit other aspects of the immune system, both specific (e.g. antibody responses) and innate (natural killer cells and granulocytes)...

..FL treatment of melanoma patients has pleiotropic clinical and hematological effects. In vivo maturation of FL-generated DCs using imiquimod may increase immune responses to tumor antigens...

..Although these reactions are believed to be immune-mediated, the antigenic targets for the cellular or humoral immune response are not known...

..This may provide DCs with ample opportunities for sensitizing tumor-specific T cells against a broad array of tumor antigen epitopes in lymph nodes...

..Our in vitro findings raise the hypothesis that if melanoma stem cells express CT antigens in vivo that immune targeting of these antigens may be a viable clinical strategy for the adjuvant treatment of melanoma...

..We evaluated persistence of immunity, relapse-free survival and tumour antigen expression upon relapse in patients vaccinated in an earlier trial...

..This study examines the clinical and immunologic efficacy of the same vaccine in patients with advanced metastatic melanoma...

..These distinct differences are of particular importance when considering the choice of DC types for clinical applications...

..The demonstrated presence of antigen-specific T cells at vaccination sites validates this method of assessing the immune response to i.d. vaccines...

..Together, our results reveal several surprising aspects of antitumor immunity and have implications for cancer vaccine design...

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..This T cell response was vaccinated in most patients who expressed HLA-DR2. This study has systematically surveyed patients vaccinated with full-length tumor antigen for a vaccinated CD4 helper T cell response...

..Low levels of expression of cancer testis antigen may indicate that they are suboptimal targets for vaccine development in desmoplastic melanoma...

..We report a first-in-man trial of a humanized antibody (hu3S193) against the Le(y) antigen...

..The pattern of anti-NY-ESO-1 T cell responses in this patient closely resembles the classical broad yet hierarchical antiviral immunity and was confirmed in a second subject...

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..These early studies have yielded a wealth of information about the immunology of NY-ESO-1 and set the scene for future clinical strategies for immune targeting of cancer...

..The ability of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor AG1478 and docetaxel chemotherapy to enhance the efficacy of RIT was also assessed in vivo...

..This will help inform decisions about selection of patients and target antigens for melanoma immunotherapy clinical trials...

..The rhIL-12 given either s.c. or i.v. was well tolerated at doses of 10-100 ng/kg. Clinical and immunological activity has been observed in this study where peptides were administered either with or without low dose rhIL-12...

..Because neither mAb bound LAGE and because there was no coordinate expression LAGE and NY-ESO-1, separate typing for each is required...

..In view of these results, further investigation of the function of CTAgs and their potential use in therapeutic targeting is warranted...

..We report on a novel method for human renal tumour transplants using an automated biopsy gun to obtain tumour tissue and an epidural needle with introducer to easily deploy the grafts under the renal capsule...

..To evaluate the accuracy of (11)C-choline PET scans in defining dominant intraprostatic lesions (DILs) for radiotherapy target volume definition...

..The favourable immune properties of KM871, combined with this preliminary clinical data, indicate that KM871 has potential for the treatment of metastatic melanoma...

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..We report final clinical and biological results of a phase II study of recombinant human IL-21 (rIL-21) in patients with metastatic melanoma...

..We hypothesized that molecular profiling could be used to identify prognostic groups within patients with stage III melanoma while also providing a greater understanding of the biological programs underpinning these differences...

..New therapeutic strategies are resulting from these emerging insights into the relationship between melanoma and the host immune response...

..Together, our results show that FoxP3, a key regulator of immune suppression, is not only expressed by Treg but also by melanoma cells, EBV-transformed B cells, and a wide variety of tumor cell lines...

..We conducted a dose escalation study combining cisplatin, irinotecan, and capecitabine (CIC), aiming to establish the maximum tolerated doses (MTD), side effect profile, and dose-limiting toxicity (DLT) of this novel regimen...

..5 mmHg. Further direct studies of renal tumour oxygenation combined with therapies directed towards hypoxia may allow a better understanding of the relationship between 18F-FMISO results and the biological significance of hypoxia in RCC...

..We hypothesized that ECSA/DPPA2 would be quiescent in most normal tissues but expressed in cancers and may therefore be a useful target for immunotherapy...

..These findings have implications for the design of peptide and protein-based vaccines...

..Culture conditions and re-stimulation time have been optimized, allowing the detection of even very rare Treg, such as those specific to tumor antigens...

..The pattern of disease in the reported patient was similar to that described in the literature, but the patient experienced a long period with untreated metastatic disease compared with that in the literature...

..Long-term therapeutic control of melanoma will require integration of specific active immunotherapy with these emerging successful therapies from the disparate fields of immune regulation and signal transduction...

..This article summarizes the current diagnostic and therapeutic use of radioisotopes for bony disease in prostate cancer with particular reference to radionuclide bone scintigraphy and positron emission tomography...

..This schedule may maximize dose intensity of both drugs with acceptable or reduced toxicity...

..This review summarizes the major published clinical trials of the new agents, discusses the controversies and research questions that have arisen as a result, and considers some of the issues that remain...

..Hypothyroidism has been observed in patients treated with sunitinib, but the mechanism whereby sunitinib induces hypothyroidism is unknown...

..Our results suggest that mIL-4 has bimodal biological roles in potentiating tumour inhibition in athymic mice: the suppression of angiogenesis and the augmentation of the host local immune response...

..This paper reviews the biology of dendritic cells and their use in clinical trials, as well as highlighting issues for future trial design...

..The purified NY-ESO-1 is being used in early stage human cancer vaccine trials in Australia and the U.S.A...

..Since it is difficult to predict the CTL responses to Melan-A peptide in a given individual, we suggest vaccinating with both Melan-A27-35 and Melan-A26-35 peptides in clinical trials...

..P2R inhibition may represent a new strategy to improve the migration of antigen-loaded DCs from the vaccination site to lymph nodes...

..CONCLUSION: FDG-PET has an important role in guiding the management of patients with advanced melanoma, particularly when surgery is contemplated...

..We will consider evidence for the current systemic therapies for muscle-invasive and metastatic disease and review the targeted therapies under investigation for advanced urothelial cancer...

..We compared the quality of common malignancy Web sites to assess them for language or disease differences and to perform a quality comparison between medical and layperson terminology...

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..In conclusion, SCM culture of melanoma does not provide a better representation of the phenotype or genotype of metastatic melanoma, and the resulting neural bias could potentially confound therapeutic target identification...

..It is essential that unusual tumors are considered when confronted by a seminal vesicle mass and that appropriate investigation and management are initiated...

..In this Opinion article we discuss some key issues common to breast and prostate cancer and how new insights into these cancers could improve patient outcomes...

..KM871 is a chimeric monoclonal antibody against the ganglioside antigen GD3, which is highly expressed on melanoma cells. We conducted an open-label, dose escalation phase I trial of KM871 in patients with metastatic melanoma...

..The objectives of this study were to determine the maximum tolerated dose (MTD) and toxicity profile of docetaxel given with G-CSF support...

..In seminoma, a negative 18F-FDG PET study correlated with a favorable clinical outcome. PET was also predictive of the response to salvage chemotherapy and was highly specific for active tumor in both NSGCT and seminoma...

..We aimed to examine the safety, pharmacokinetics, and biological effects of recombinant human LIF (rhLIF, emfilermin) in patients with advanced cancer...

..Here we report the effects of systemic IL-21 therapy on the immune system in two phase 1 trials with this novel cytokine...

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