CAR-T cell. the long and winding road to solid tumors

Adoptive cell therapy of solid tumors with reprogrammed T cells can be considered the "next generation" of cancer hallmarks. CAR-T cells fail to be as effective as in liquid tumors for the inability to reach and survive in the microenvironment surrounding the neoplastic foci. The intricate net of cross-interactions occurring between tumor components, stromal and immune cells leads to an ineffective anergic status favoring the evasion from the host's defenses. Our goal is hereby to trace the road imposed by solid tumors to CAR-T cells, highlighting pitfalls and strategies to be developed and refined to possibly overcome these hurdles

A Delphi study and ranking exercise to support commissioning services:Future delivery of Thrombectomy services in England

Background: Intra-arterial thrombectomy is the gold standard treatment for large artery occlusive stroke. However, the evidence of its benefits is almost entirely based on trials delivered by experienced neurointerventionists working in established teams in neuroscience centres. Those responsible for the design and prospective reconfiguration of services need access to a comprehensive and complementary array of information on which to base their decisions. This will help to ensure the demonstrated effects from trials may be realised in practice and account for regional/local variations in resources and skill-sets. One approach to elucidate the implementation preferences and considerations of key experts is a Delphi survey. In order to support commissioning decisions, we aimed to using an electronic Delphi survey to establish consensus on the options for future organisation of thrombectomy services among physicians with clinical experience in managing large artery occlusive stroke. Methods: A Delphi survey was developed with 12 options for future organisation of thrombectomy services in England. A purposive sampling strategy established an expert panel of stroke physicians from the British Association of Stroke Physicians (BASP) Clinical Standards and/or Executive Membership that deliver 24/7 intravenous thrombolysis. Options with aggregate scores falling within the lowest quartile were removed from the subsequent Delphi round. Options reaching consensus following the two Delphi rounds were then ranked in a final exercise by both the wider BASP membership and the British Society of Neuroradiologists (BSNR). Results: Eleven stroke physicians from BASP completed the initial two Delphi rounds. Three options achieved consensus, with subsequently wider BASP (97%, n=43) and BSNR members (86%, n=21) assigning the highest approval rankings in the final exercise for transferring large artery occlusive stroke patients to nearest neuroscience centre for thrombectomy based on local CT/CT Angiography. Conclusions: The initial Delphi rounds ensured optimal reduction of options by an expert panel of stroke physicians, while subsequent ranking exercises allowed remaining options to be ranked by a wider group of experts within stroke to reach consensus. The preferred implementation option for thrombectomy is conveying suspected stroke patients for CT/CT Angiography and secondary transfer of large artery occlusive stroke patients to the nearest neuroscience centre

Dendritic cell vaccines for high-grade gliomas

Matthew E Eagles,1 Farshad Nassiri,2,3 Jetan H Badhiwala,2 Suganth Suppiah,2 Saleh A Almenawer,4 Gelareh Zadeh,3,5 Kenneth D Aldape3,6 1Section of Neurosurgery, Department of Clinical Neurosciences, University of Calgary, Calgary, AB, Canada; 2Division of Neurosurgery, Department of Surgery, University of Toronto, Toronto, ON, Canada; 3MacFeeters-Hamilton Neuro-Oncology Program, University Health Network, Toronto, ON, Canada; 4Division of Neurosurgery, Department of Surgery, McMaster University, Hamilton, ON, Canada; 5Division of Neurosurgery, University Health Network, Toronto, ON, Canada; 6Division of Pathology, University Health Network, Toronto, ON, Canada Abstract: Glioblastoma (GBM) is the most common and fatal primary adult brain tumor. To date, various promising chemotherapeutic regimens have been trialed for use in GBM; however, temozolomide (TMZ) therapy remains the only US Food and Drug Administration-approved first-line chemotherapeutic option for newly diagnosed GBM. Despite maximal therapy with surgery and combined concurrent chemoradiation and adjuvant TMZ therapy, the median overall survival remains approximately 14 months. Given the failure of conventional chemotherapeutic strategies in GBM, there has been renewed interest in the role of immunotherapy in GBM. Dendritic cells are immune antigen-presenting cells that play a role in both the innate and adaptive immune system, thereby making them prime vehicles for immunotherapy via dendritic cell vaccinations (DCVs) in various cancers. There is great enthusiasm surrounding the use of DCVs for GBM with multiple ongoing trials. In this review, we comprehensively summarize the safety, efficacy, and quality of life results from 33 trials reporting on DCV for high-grade gliomas. Keywords: glioma, vaccine, dendritic cells, glioblastom