Radioimmunotherapy of B-cell lymphoma with radiolabelled anti-CD20 monoclonal antibodies

CD20 has proven to be an excellent target for the treatment of B-cell lymphoma, first for the chimeric monoclonal antibody rituximab (Rituxan™), and more recently for the radiolabelled antibodies Y-90 ibritumomab tiuxetan (Zevalin™) and I-131 tositumomab (Bexxar™). Radiation therapy effects are due to beta emissions with path lengths of 1–5 mm; gamma radiation emitted by I-131 is the only radiation safety issue for either product. Dose-limiting toxicity for both radiolabelled antibodies is reversible bone marrow suppression. They produce response rates of 70%–90% in low-grade and follicular lymphoma and 40%–50% in transformed low-grade or intermediate-grade lymphomas. Both products produce higher response rates than related unlabelled antibodies, and both are highly active in patients who are relatively resistant to rituximab-based therapy. Median duration of response to a single course of treatment is about 1 year with complete remission rates that last 2 years or longer in about 25% of patients. Clinical trials suggest that anti- CD20 radioimmunotherapy is superior to total body irradiation in patients undergoing stem cell supported therapy for B-cell lymphoma, and that it is a safe and efficacious modality when used as consolidation therapy following chemotherapy. Among cytotoxic treatment options, current evidence suggests that one course of anti-CD20 radioimmunotherapy is as efficacious as six to eight cycles of combination chemotherapy. A major question that persists is how effective these agents are in the setting of rituximab- refractory lymphoma. These products have been underutilised because of the complexity of treatment coordination and concerns regarding reimbursement

The Case for a New Frontiers-Class Uranus Orbiter: System Science at an Underexplored and Unique World with a Mid-scale Mission

Current knowledge of the Uranian system is limited to observations from the flyby of Voyager 2 and limited remote observations. However, Uranus remains a highly compelling scientific target due to the unique properties of many aspects of the planet itself and its system. Future exploration of Uranus must focus on cross-disciplinary science that spans the range of research areas from the planet's interior, atmosphere, and magnetosphere to the its rings and satellites, as well as the interactions between them. Detailed study of Uranus by an orbiter is crucial not only for valuable insights into the formation and evolution of our solar system but also for providing ground truths for the understanding of exoplanets. As such, exploration of Uranus will not only enhance our understanding of the ice giant planets themselves but also extend to planetary dynamics throughout our solar system and beyond. The timeliness of exploring Uranus is great, as the community hopes to return in time to image unseen portions of the satellites and magnetospheric configurations. This urgency motivates evaluation of what science can be achieved with a lower-cost, potentially faster-turnaround mission, such as a New Frontiers–class orbiter mission. This paper outlines the scientific case for and the technological and design considerations that must be addressed by future studies to enable a New Frontiers–class Uranus orbiter with balanced cross-disciplinary science objectives. In particular, studies that trade scientific scope and instrumentation and operational capabilities against simpler and cheaper options must be fundamental to the mission formulation

Defining the Critical Hurdles in Cancer Immunotherapy

ABSTRACT: Scientific discoveries that provide strong evidence of antitumor effects in preclinical models often encounter significant delays before being tested in patients with cancer. While some of these delays have a scientific basis, others do not. We need to do better. Innovative strategies need to move into early stage clinical trials as quickly as it is safe, and if successful, these therapies should efficiently obtain regulatory approval and widespread clinical application. In late 2009 and 2010 the Society for Immunotherapy of Cancer (SITC), convened an "Immunotherapy Summit" with representatives from immunotherapy organizations representing Europe, Japan, China and North America to discuss collaborations to improve development and delivery of cancer immunotherapy. One of the concepts raised by SITC and defined as critical by all parties was the need to identify hurdles that impede effective translation of cancer immunotherapy. With consensus on these hurdles, international working groups could be developed to make recommendations vetted by the participating organizations. These recommendations could then be considered by regulatory bodies, governmental and private funding agencies, pharmaceutical companies and academic institutions to facilitate changes necessary to accelerate clinical translation of novel immune-based cancer therapies. The critical hurdles identified by representatives of the collaborating organizations, now organized as the World Immunotherapy Council, are presented and discussed in this report. Some of the identified hurdles impede all investigators, others hinder investigators only in certain regions or institutions or are more relevant to specific types of immunotherapy or first-in-humans studies. Each of these hurdles can significantly delay clinical translation of promising advances in immunotherapy yet be overcome to improve outcomes of patients with cancer