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

Development and characterization of a rabbit alveolar bone nonhealing defect model.

Item does not contain fulltextThe aim of this study was to develop an easily accessible and reproducible, nonhealing alveolar bone defect in the rabbit mandible. Twenty-four adult male New Zealand white rabbits underwent unilateral mandibular defect surgery. Two types of defect in the premolar/molar region were compared: (1) a 10-mm "full thickness" cylindrical defect removing both cortical plates and the intervening trabecular bone and tooth roots; (2) a 10-mm "partial thickness" cylindrical defect removing only the lateral bony cortex, trabecular bone, and tooth roots. Both types of defect were examined at 0, 8, and 16 weeks using histology and/or microcomputed tomography to determine the quality and quantity of bone formation. The partial thickness defect displayed significant bone fill at 8 weeks (86.9% +/- 10.8%), and complete regeneration of bony contours and bridging by 16 weeks. In contrast, the full thickness defect was never able to bridge itself and displayed no significant difference in bone regeneration between the 8-week (61.5% +/- 3.7%) and 16-week (55.1% +/- 18.5%) time points. These results indicate that a nonhealing defect can be created with a 10-mm bicortical cylindrical ostectomy placed in the premolar/molar region of the rabbit mandible, demonstrating the potential of this animal model as a test bed for mandibular biomaterials and tissue-engineering constructs

Development and characterization of a rabbit alveolar bone nonhealing defect model.

The aim of this study was to develop an easily accessible and reproducible, nonhealing alveolar bone defect in the rabbit mandible. Twenty-four adult male New Zealand white rabbits underwent unilateral mandibular defect surgery. Two types of defect in the premolar/molar region were compared: (1) a 10-mm "full thickness" cylindrical defect removing both cortical plates and the intervening trabecular bone and tooth roots; (2) a 10-mm "partial thickness" cylindrical defect removing only the lateral bony cortex, trabecular bone, and tooth roots. Both types of defect were examined at 0, 8, and 16 weeks using histology and/or microcomputed tomography to determine the quality and quantity of bone formation. The partial thickness defect displayed significant bone fill at 8 weeks (86.9% +/- 10.8%), and complete regeneration of bony contours and bridging by 16 weeks. In contrast, the full thickness defect was never able to bridge itself and displayed no significant difference in bone regeneration between the 8-week (61.5% +/- 3.7%) and 16-week (55.1% +/- 18.5%) time points. These results indicate that a nonhealing defect can be created with a 10-mm bicortical cylindrical ostectomy placed in the premolar/molar region of the rabbit mandible, demonstrating the potential of this animal model as a test bed for mandibular biomaterials and tissue-engineering constructs

Receptor cells in Ips typographus and Dendroctonus micans specific to pheromones of the reciprocal genus

SCOPUS: ar.jinfo:eu-repo/semantics/publishe