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

Defining the critical hurdles in cancer immunotherapy

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 if overcome, have the potential to improve outcomes of patients with cancer

Determining crystal structures through crowdsourcing and coursework

We show here that computer game players can build high-quality crystal structures. Introduction of a new feature into the computer game Foldit allows players to build and real-space refine structures into electron density maps. To assess the usefulness of this feature, we held a crystallographic model-building competition between trained crystallographers, undergraduate students, Foldit players and automatic model-building algorithms. After removal of disordered residues, a team of Foldit players achieved the most accurate structure. Analysing the target protein of the competition, YPL067C, uncovered a new family of histidine triad proteins apparently involved in the prevention of amyloid toxicity. From this study, we conclude that crystallographers can utilize crowdsourcing to interpret electron density information and to produce structure solutions of the highest quality

Poisonings and clinical toxicology: a template for Ireland.

Background Poisons information is accessed around the clock in the British Isles from six centres of which two are in Ireland at Dublin and Belfast accompanied by consultant toxicologist advisory service. The numbers of calls in Ireland are down to about 40 per day due to easy access to online data bases. Access to Toxbase, the clinical toxicology database of the National Poisons Information Service is available to National Health Service (NHS) health professionals and to Emergency Departments and Intensive Care units in the Republic of Ireland. There are 59 Toxbase users in the Republic of Ireland and 99 % of activity originates in Emergency Departments. All United States Poison Control Centres primarily use Poisindex which is a commercial database from Thomson Reuters. Results Information on paracetamol, diazepam, analgesics and psycho-active compounds are the commonest queries. Data from telephone and computer accesses provide an indicator of future trends in both licit and illicit drug poisons which may direct laboratory analytical service developments. Data from National Drug-Related Deaths Index is the most accurate information on toxicological deaths in Ireland. Laboratory toxicology requirements to support emergency departments are listed

Cannabis smoking and myocardial infarction.

Letter to the editor: Cannabis as a trigger for myocardial infarction has a population attributable fraction (PAF) of 0.8% (99% confidence interval 0.38–1.67%) even though it is the most widely used illicit drug.. Objective evidence restricts the triggering period to the first 2h after cannabis smoking..

Biochemical toxicology and suicide in Ireland: a laboratory study.

Biochemical toxicology in suicides provides a template to improve preventive interventions in cases of suicide. The menu for biochemical toxicological analysis in coroners’ cases is not prescriptive in Ireland or in the United Kingdom. The aim of the study was to confirm that reliance on the results of an immunoassay screen for drugs of abuse and common analgesics in order to select samples for compound confirmation by gas chromatography-mass spectrometry is likely to understate the potential role of drugs in suicide. Blood and urine samples were analyzed using enzyme immunoassay, alcohols by gas chromatography and urines were screened by Bio-Rad’s Rapid Emergency Drug Identification (REMEDi) system. Laboratory data from analysis of 132 cases of suicide, including 101 cases of hanging revealed that 83 % were male confirming suicide as a male epidemic. Overall, alcohol was a factor in 57 %, benzodiazepines in 26 %, cannabinoids in 11 %, opioids in 19.7 %, sympathomimetics in 7.5 %, cocaine in 4.5 %, antidepressants 22 %, antipsychotics in 10 %, hypnotics in 5 %, and antihistamines in 4 % of these cases. Screening compounds in cases of hanging and other suicides should extend beyond the narrow focus of alcohol and illicit drugs to include a wide spectrum of psychoactive and other compounds as a standard procedure. The wide range of licit and illicit compounds found in these cases reflects current experience and dictates the necessity for chromatographic screening with mass spectroscopy confirmation in all cases as best practice