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

Spinal Cord Infarction in a Patient with Hereditary Spherocytosis: A Case Report and Discussion

The etiology of spinal cord infarcts (SCIs), besides being related to aortic perioperative events, in large subset of SCIs, remains cryptogenic. We present a first case of SCI in a patient with hereditary spherocytosis and discuss the potential pathophysiologic considerations for vascular compromise. A 43-year-old woman with a history of hereditary spherocytosis, post splenectomy status, presented with chest, back, and shoulder pain with subsequent myelopathic picture; SCI extending from C4-T2 was confirmed by MRI. Despite aggressive treatment her stroke progressed leading to her demise. Her autopsy confirmed the SCI and revealed some incidental findings, but the cause of SCI remained unidentified. Exclusion of the known etiologies of SCI by extensive negative workup including autopsy evaluation suggested that SCI in our case was related to her history of hereditary spherocytosis. Both venous and arterial adverse vascular events, at a higher rate, have been associated in patients with hereditary spherocytosis who had their spleens removed compared to nonsplenectomized patients. Postsplenectomy increases in the platelet, red blood cell count, leukocyte count, and cholesterol concentrations are postulated to contribute to increased thrombotic risk. Additional prothrombotic factors include continuous platelet activation and adhesion as well as abnormalities of the red blood cell membrane