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

Multi-trait genome-wide association study identifies new loci associated with optic disc parameters

A new avenue of mining published genome-wide association studies includes the joint analysis of related traits. The power of this approach depends on the genetic correlation of traits, which reflects the number of pleiotropic loci, i.e. genetic loci influencing multiple traits. Here, we applied new meta-analyses of optic nerve head (ONH) related traits implicated in primary open-angle glaucoma (POAG); intraocular pressure and central corneal thickness using Haplotype reference consortium imputations. We performed a multi-trait analysis of ONH parameters cup area, disc area and vertical cup-disc ratio. We uncover new variants; rs11158547 in PPP1R36-PLEKHG3 and rs1028727 near SERPINE3 at genome-wide significance that replicate in independent Asian cohorts imputed to 1000 Genomes. At this point, validation of these variants in POAG cohorts is hampered by the high degree of heterogeneity. Our results show that multi-trait analysis is a valid approach to identify novel pleiotropic variants for ONH

Regionale Parkeerstudie Twentse Steden

De Twentse gemeenten Almelo, Enschede, Hengelo en Oldenzaal bezinnen zich op mogelijkheden om de groei van het autoverkeer te beheersen. Een gemeenschappelijke aanpak (met parkeerbeleid als belangrijke sturende factor) acht men noodzakelijk. De gemeenten laten een regionale parkeerstudie uitvoeren, die zich richt op de doelgroepen bewoners, bezoekers en werknemers/bedrijven, longitudinaal van karakter is en verschillende (deel)onderzoeken omvat. Deze paper omvat de eerste resultaten van de studie. Enschede en Hengelo lijken meer een noodzaak te zien tot terugdringing van de automobiliteit dan Almelo en Oldenzaal. Eigenbelangen lijken afstemming van parkeerbeleid de gemeenten in de weg te staan. Uitbreiding van betaald parkeren en verhoging van de tarieven hebben in Enschede niet geleid tot lagere parkeerbezettingen. De verandering van de parkeersituatie lijkt evenmin tot een verandering in de vervoerwijzekeuze (van bezoekers en werknemers) te hebben geleid. Leeftijd en (te overbruggen afstand bepalen mede het vervoerwijzekeuzegedrag