Dataset Information

Fit-For-Purpose PD-L1 Biomarker Testing For Patient Selection in Immuno-Oncology: Guidelines For Clinical Laboratories From the Canadian Association of Pathologists-Association Canadienne Des Pathologistes (CAP-ACP).

ABSTRACT: Since 2014, programmed cell death protein 1 (PD-1)/programmed cell death ligand 1 (PD-L1) checkpoint inhibitors have been approved by various regulatory agencies for the treatment of multiple cancers including melanoma, lung cancer, urothelial carcinoma, renal cell carcinoma, head and neck cancer, classical Hodgkin lymphoma, colorectal cancer, gastroesophageal cancer, hepatocellular cancer, and other solid tumors. Of these approved drug/disease combinations, a subset also has regulatory agency-approved, commercially available companion/complementary diagnostic assays that were clinically validated using data from their corresponding clinical trials. The objective of this document is to provide evidence-based guidance to assist clinical laboratories in establishing fit-for-purpose PD-L1 biomarker assays that can accurately identify patients with specific tumor types who may respond to specific approved immuno-oncology therapies targeting the PD-1/PD-L1 checkpoint. These recommendations are issued as 38 Guideline Statements that address (i) assay development for surgical pathology and cytopathology specimens, (ii) reporting elements, and (iii) quality assurance (including validation/verification, internal quality assurance, and external quality assurance). The intent of this work is to provide recommendations that are relevant to any tumor type, are universally applicable and can be implemented by any clinical immunohistochemistry laboratory performing predictive PD-L1 immunohistochemistry testing.

SUBMITTER: Cheung CC

PROVIDER: S-EPMC6887625 | biostudies-literature | 2019 Nov/Dec

REPOSITORIES: biostudies-literature

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Publications

Fit-For-Purpose PD-L1 Biomarker Testing For Patient Selection in Immuno-Oncology: Guidelines For Clinical Laboratories From the Canadian Association of Pathologists-Association Canadienne Des Pathologistes (CAP-ACP).

Cheung Carol C CC Barnes Penny P Bigras Gilbert G Boerner Scott S Butany Jagdish J Calabrese Fiorella F Couture Christian C Deschenes Jean J El-Zimaity Hala H Fischer Gabor G Fiset Pierre O PO Garratt John J Geldenhuys Laurette L Gilks C Blake CB Ilie Marius M Ionescu Diana D Lim Hyun J HJ Manning Lisa L Mansoor Adnan A Riddell Robert R Ross Catherine C Roy-Chowdhuri Sinchita S Spatz Alan A Swanson Paul E PE Tron Victor A VA Tsao Ming-Sound MS Wang Hangjun H Xu Zhaolin Z Torlakovic Emina E EE

Applied immunohistochemistry & molecular morphology : AIMM 20191101 10

Since 2014, programmed cell death protein 1 (PD-1)/programmed cell death ligand 1 (PD-L1) checkpoint inhibitors have been approved by various regulatory agencies for the treatment of multiple cancers including melanoma, lung cancer, urothelial carcinoma, renal cell carcinoma, head and neck cancer, classical Hodgkin lymphoma, colorectal cancer, gastroesophageal cancer, hepatocellular cancer, and other solid tumors. Of these approved drug/disease combinations, a subset also has regulatory agency-a ...[more]

PMID: 31584451

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Project description:Rationale, aims and objectivesThe field of implementation science is critical for embedding research evidence into healthcare practice, benefiting individuals, organizations, governments, and the broader community. Implementation science is messy and complex, underpinned by many theories and frameworks. Efficacious interventions for older people with multiple comorbidities exist, yet many lack effectiveness evaluation relevant to pragmatic implementation within aged care practice. This article outlines the conceptualization and development of an Implementation Framework for Aged Care (IFAC), fit-for-purpose for an aged care organization, Bolton Clarke, intent on embedding evidence into practice.MethodA four-stage process was adopted to (1) explore context and relevant literature to conceptualize the IFAC; (2) identify key elements for a draft IFAC; (3) expand elements and refine the draft in consultation with experts and (4) apply the IFAC to three existing projects, identifying key learnings. A checklist to operationalize the IFAC was then developed.ResultsThe IFAC is grounded in codesign principles and encapsulated by the implementation context, from a social, cultural and political perspective. The IFAC addresses the questions of (1) why do we need to change?; (2) what do we know?; (3) who will benefit?; (4) who will make the change?; (5) what strategies will be used?; and (6) what difference are we making? Three pilot projects: early adoption of a Wellness and Reablement approach; a care worker and virtual physiotherapist-led program to prevent falls; and a therapeutic horticulture program for residential communities, highlight learnings of applying the IFAC in practice.ConclusionThis fit-for-purpose IFAC was developed for a proactive and responsive aged care provider. The simplicity of the six-question IFAC is underpinned by substantial theoretical perspectives for its elements and their connections. This complexity is then consolidated into an 18-question checklist to operationalize the IFAC, necessary to advance the translation of evidence into clinical practice.

Project description:Exosomes are defined as submicron (30-150 nm), lipid bilayer-enclosed extracellular vesicles (EVs), specifically generated by the late endosomal compartment through fusion of multivesicular bodies with the plasma membrane. Produced by almost all cells, exosomes were originally considered to represent just a mechanism for jettisoning unwanted cellular moieties. Although this may be a major function in most cells, evolution has recruited the endosomal membrane-sorting pathway to duties beyond mere garbage disposal, one of the most notable examples being its cooption by retroviruses for the generation of Trojan virions. It is, therefore, tempting to speculate that certain cell types have evolved an exosome subclass active in intracellular communication. We term this EV subclass "signalosomes" and define them as exosomes that are produced by the "signaling" cells upon specific physiological or environmental cues and harbor cargo capable of modulating the programming of recipient cells. Our recent studies have established that signalosomes released by mesenchymal stem/stromal cells (MSCs) represent the main vector of MSC immunomodulation and therapeutic action in animal models of lung disease. The efficacy of MSC-exosome treatments in a number of preclinical models of cardiovascular and pulmonary disease supports the promise of application of exosome-based therapeutics across a wide range of pathologies within the near future. However, the full realization of exosome therapeutic potential has been hampered by the absence of standardization in EV isolation, and procedures for purification of signalosomes from the main exosome population. This is mainly due to immature methodologies for exosome isolation and characterization and our incomplete understanding of the specific characteristics and molecular composition of signalosomes. In addition, difficulties in defining metrics for potency of exosome preparations and the challenges of industrial scale-up and good manufacturing practice compliance have complicated smooth and timely transition to clinical development. In this manuscript, we focus on cell culture conditions, exosome harvesting, dosage, and exosome potency, providing some empirical guidance and perspectives on the challenges in bringing exosome-based therapies to clinic.

Project description:Compliance with guideline removal targets for Cryptosporidium which do not provide any credit for the inactivation of oocysts through wastewater treatment processes can considerably increase the cost of providing recycled water. Here we present the application of an integrated assay to quantify both oocyst numbers and infectivity levels after various treatment stages at three Victorian and two South Australian (SA) wastewater treatment plants (WWTPs). Oocyst density in the raw sewage was commensurate with community disease burden, with early rounds of sampling capturing a widespread cryptosporidiosis outbreak in Victoria. The level of infectivity of oocysts in sewage was stable throughout the year but was significantly lower at the SA WWTPs. Removals across secondary treatment processes were seasonal, with poorer removals associated with inflow variability; however, no decrease in the oocyst infectivity was identified. For SA WWTPs, those oocysts remaining within the secondary treatment-clarified effluent were proportionally more infectious than those in raw sewage. Lagoon systems demonstrated significant inactivation or removal of oocysts, with attenuation being seasonal. Examination of a UV system emphasized its efficacy as a disinfectant barrier but conversely confirmed the importance of a multibarrier approach with the detection of infectious oocysts postdisinfection. The ability to characterize risk from infectious oocysts revealed that the risk from Cryptosporidium is significantly lower than previously thought and that its inclusion in quantitative risk assessments of reuse systems will more accurately direct the selection of treatment strategies and capital expenditure, influencing the sustainability of such schemes.IMPORTANCE Here we present the application of a recently developed integrated assay not only to quantify the removal of Cryptosporidium oocysts but also to quantify their infectivity across various treatment stages at five wastewater treatment plants (WWTPs), thereby better measuring the "true effect" of the treatment train on oocyst risk reduction. For a number of the WWTPs analyzed in this study the risk, is significantly lower than previously thought. Therefore, the inclusion of oocyst infectivity in guideline values and in quantitative microbial risk assessment (QMRA) has the potential to affect future treatment directions and capital expenditure.

Dataset Information

Fit-For-Purpose PD-L1 Biomarker Testing For Patient Selection in Immuno-Oncology: Guidelines For Clinical Laboratories From the Canadian Association of Pathologists-Association Canadienne Des Pathologistes (CAP-ACP).

Publications

Fit-For-Purpose PD-L1 Biomarker Testing For Patient Selection in Immuno-Oncology: Guidelines For Clinical Laboratories From the Canadian Association of Pathologists-Association Canadienne Des Pathologistes (CAP-ACP).

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