• 5T4 as a target for immunotherapy in renal cell carcinoma.

      Elkord, Eyad; Shablak, Alaaeldin; Stern, Peter L; Hawkins, Robert E (2009-12)
    • Maintenance and consolidation therapy in patients with unresectable stage III/IV non-small cell lung cancer.

      Thatcher, Nick; Heighway, Jim; Department of Medical Oncology, Christie Hospital NHS Trust, Wilmslow Road, Manchester M20 4BX, United Kingdom. nick.thatcher@christie.nhs.uk (2010)
      Globally, lung cancer is the leading cause of cancer-related mortality. Current chemotherapy combinations for the first-line treatment of advanced disease (stage IIIB with malignant pleural effusion/stage IV) and chemoradiotherapy regimens for the treatment of unresectable locally advanced disease (stage IIIA and IIIB without malignant pleural effusion) appear to have reached an efficacy plateau. The addition of new compounds including targeted agents to standard first-line cytotoxic doublets, administered concurrently and/or as maintenance therapy in patients who have not experienced disease progression after such treatment, has been shown to improve efficacy beyond this plateau in patients with advanced disease. However, to date, such approaches have been less successful in the treatment of patients with unresectable locally advanced stage III disease. The purpose of this review is to summarize the data from recent randomized phase III studies involving agents administered as maintenance or consolidation therapy in the treatment of unresectable stage III/IV non-small cell lung cancer (NSCLC). A possible alternative approach to the use of cytotoxic or molecularly targeted agents in this setting is the administration of therapeutic anticancer vaccines, which are designed to stimulate a host immunological response against the tumor. Current data in relation to the potential of vaccine therapy for NSCLC are therefore also reviewed, with a particular focus on belagenpumatucel-L and L-BLP25 vaccines, which are currently undergoing phase III evaluation as maintenance therapies in patients with unresectable stage III/IV NSCLC who have tumor control following first-line therapy.
    • Systemic therapy for metastatic malignant melanoma--from deeply disappointing to bright future?

      Lorigan, Paul C; Eisen, Tim; Hauschild, Axel; CRUK Department of Medical Oncology, Christie Hospital NHS Trust, Wilmslow Road, Manchester, UK. paul.lorigan@manchester.ac.uk (2008-05)
      The last decade has seen a considerable improvement in the understanding of the biology of melanoma. Advances have come in the understanding of the importance of critical oncogenes and tumour suppressor genes, epigenetic phenomena, signalling pathways, drug resistance mechanisms, the pivotal role of the local immune system, and the importance of cell-cell and cell-matrix interactions. Many of these pathways and interactions include potentially 'drugable' targets. These developments have allowed the identification and/or design of a range of new, targeted therapies. Evaluation of these new drugs has brought a whole new series of challenges. These include identification of appropriate pre-clinical models, overcoming the redundancy in-built in complex biological systems, identification of appropriate molecular and clinical endpoints to show that the drug is hitting the target, how to combine treatments, and new toxicities. For the first time, there is the possibility of personalized treatment for melanoma patients, based on individual host and tumour characteristics. This paper discusses the range of new drugs and targets have been identified, the outcome of clinical trials, and the directions for future advances.
    • T cell-based immunotherapy of metastatic renal cell carcinoma: modest success and future perspective.

      Shablak, Alaaeldin; Hawkins, Robert E; Rothwell, Dominic G; Elkord, Eyad; Department of Medical Oncology, School of Cancer, Enabling Sciences and Technology, The University of Manchester, Manchester Academic Health Science Centre, The Christie NHS Foundation Trust, Manchester, United Kingdom. (2009-11-01)
      Metastatic renal cell carcinoma (MRCC) remains a challenging malignancy to treat. Cancer immunotherapies have been extensively explored in melanoma and RCC as they poorly respond to conventional cytotoxic agents but show responses to a variety of immunologic agents. The recent considerable success of T cell-based immunotherapy in melanoma warrants further efforts to apply this treatment to other cancers including MRCC. Although RCC is an immunosensitive cancer, similar attempts in MRCC have shown a very limited success. In this review, we summarize the clinical data on T cell-based immunotherapies for MRCC showing the modest success that has been achieved to date. More importantly, we discuss potential strategies for improving its efficacy for the treatment of MRCC in light of the important achievements for treating metastatic melanoma. In particular, the growing evidence of success by combining expanded tumor-infiltrating lymphocytes with lymphodepletion merits investigation in MRCC. Identifying new RCC-associated antigens, optimized methods, and conditions for detection, isolation, and/or modification and expansion of tumor-specific T cells are all important strategies to be pursued for improving T cell-based immunotherapy of MRCC.