The Society for Immunotherapy of Cancer perspective on regulation of interleukin-6 signaling in COVID-19-related systemic inflammatory response

The pandemic caused by the novel coronavirus SARS-CoV-2 has placed an unprecedented burden on healthcare systems around the world. In patients who experience severe disease, acute respiratory distress is often accompanied by a pathological immune reaction, sometimes referred to as ‘cytokine storm’. One hallmark feature of the profound inflammatory state seen in patients with COVID-19 who succumb to pneumonia and hypoxia is marked elevation of serum cytokines, especially interferon gamma, tumor necrosis factor alpha, interleukin 17 (IL-17), interleukin 8 (IL-8) and interleukin 6 (IL-6). Initial experience from the outbreaks in Italy, China and the USA has anecdotally demonstrated improved outcomes for critically ill patients with COVID-19 with the administration of cytokine-modulatory therapies, especially anti-IL-6 agents. Although ongoing trials are investigating anti-IL-6 therapies, access to these therapies is a concern, especially as the numbers of cases worldwide continue to climb. An immunology-informed approach may help identify alternative agents to modulate the pathological inflammation seen in patients with COVID-19. Drawing on extensive experience administering these and other immune-modulating therapies, the Society for Immunotherapy of Cancer offers this perspective on potential alternatives to anti-IL-6 that may also warrant consideration for management of the systemic inflammatory response and pulmonary compromise that can be seen in patients with severe COVID-19

Infant Botulism

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66984/2/10.1177_000992289303201105.pd

A systematic approach to biomarker discovery; Preamble to "the iSBTc-FDA taskforce on immunotherapy biomarkers"

The International Society for the Biological Therapy of Cancer (iSBTc) has initiated in collaboration with the United States Food and Drug Administration (FDA) a programmatic look at innovative avenues for the identification of relevant parameters to assist clinical and basic scientists who study the natural course of host/tumor interactions or their response to immune manipulation. The task force has two primary goals: 1) identify best practices of standardized and validated immune monitoring procedures and assays to promote inter-trial comparisons and 2) develop strategies for the identification of novel biomarkers that may enhance our understating of principles governing human cancer immune biology and, consequently, implement their clinical application. Two working groups were created that will report the developed best practices at an NCI/FDA/iSBTc sponsored workshop tied to the annual meeting of the iSBTc to be held in Washington DC in the Fall of 2009. This foreword provides an overview of the task force and invites feedback from readers that might be incorporated in the discussions and in the final document

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

Emerging concepts in biomarker discovery; The US-Japan workshop on immunological molecular markers in oncology

Supported by the Office of International Affairs, National Cancer Institute (NCI), the "US-Japan Workshop on Immunological Biomarkers in Oncology" was held in March 2009. The workshop was related to a task force launched by the International Society for the Biological Therapy of Cancer (iSBTc) and the United States Food and Drug Administration (FDA) to identify strategies for biomarker discovery and validation in the field of biotherapy. The effort will culminate on October 28th 2009 in the "iSBTc-FDA-NCI Workshop on Prognostic and Predictive Immunologic Biomarkers in Cancer", which will be held in Washington DC in association with the Annual Meeting. The purposes of the US-Japan workshop were a) to discuss novel approaches to enhance the discovery of predictive and/or prognostic markers in cancer immunotherapy; b) to define the state of the science in biomarker discovery and validation. The participation of Japanese and US scientists provided the opportunity to identify shared or discordant themes across the distinct immune genetic background and the diverse prevalence of disease between the two Nations

Combination immunotherapy: a road map

Cancer immunotherapy and in particular monoclonal antibodies blocking the inhibitory programed cell death 1 pathway (PD-1/PD-L1) have made a significant impact on the treatment of cancer patients in recent years. However, despite the remarkable clinical efficacy of these agents in a number of malignancies, it has become clear that they are not sufficiently active for many patients. Initial evidence, for example with combined inhibition of PD-1 and CTLA-4 in melanoma and non-small cell lung cancer (NSCLC), has highlighted the potential to further enhance the clinical benefits of monotherapies by combining agents with synergistic mechanisms of action. In order to address the current progress and consider challenges associated with these novel approaches, the Society for Immunotherapy of Cancer (SITC) convened a Combination Immunotherapy Task Force. This Task Force was charged with identifying and prioritizing the most promising prospects for combinatorial approaches as well as addressing the challenges associated with developing these strategies. As a result of the extensive clinical benefit and tolerable side effects demonstrated with agents inhibiting the PD-1 pathway, an overview of current evidence to support its promising potential for use as a backbone in combination strategies is presented. In addition, key issues in the development of these strategies including preclinical modeling, patient safety and toxicity considerations, clinical trial design, and endpoints are also discussed. Overall, the goal of this manuscript is to provide a summary of the current status and potential challenges associated with the development and clinical implementation of these strategies