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  1. Article ; Online: Current approaches to evaluate the function of cytotoxic T-cells in non-human primates.

    Kamperschroer, Cris / Frank, Brendon / Genell, Caroline / Lebrec, Hervé / Mitchell-Ryan, Shermaine / Molinier, Brigitte / Newsome, Courtni / Piche, Marie-Soleil / Weinstock, Daniel / Collinge, Mark / Freebern, Wendy / Rubio, Daniel

    Journal of immunotoxicology

    2023  Volume 20, Issue 1, Page(s) 2176952

    Abstract: Cytotoxic T-lymphocytes (CTL) are a subset of T-cells that play a critical role in protecting against intracellular infections and cancer, and have the ability to identify and kill infected or transformed cells expressing non-self peptides associated ... ...

    Abstract Cytotoxic T-lymphocytes (CTL) are a subset of T-cells that play a critical role in protecting against intracellular infections and cancer, and have the ability to identify and kill infected or transformed cells expressing non-self peptides associated with major histocompatibility (MHC) Class I molecules. Conversely, aberrant CTL activity can contribute to immune-related pathology under conditions of overwhelming infection or autoimmunity. Disease-modifying therapeutics can have unintended effects on CTL, and a growing number of therapeutics are intended to either suppress or enhance CTL or their functions. The susceptibility of CTL to unintended effects from common therapeutic modalities underscores the need for a better understanding of the impact that such therapies have on CTL function and the associated safety implications. While there are reliable ways of quantifying CTL, notably via flow cytometric analysis of specific CTL markers, it has been a greater challenge to implement fit-for-purpose methods measuring CTL function in the context of safety studies of therapeutics. This review focuses on methods for measuring CTL responses in the context of drug safety and pharmacology testing, with the goals of informing the reader about current approaches, evaluating their pros and cons, and providing perspectives on the utility of these approaches for safety evaluation.
    MeSH term(s) Animals ; T-Lymphocytes, Cytotoxic ; Primates ; Neoplasms/therapy ; Cytotoxicity, Immunologic
    Language English
    Publishing date 2023-02-01
    Publishing country England
    Document type Review ; Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2205064-4
    ISSN 1547-6901 ; 1547-691X
    ISSN (online) 1547-6901
    ISSN 1547-691X
    DOI 10.1080/1547691X.2023.2176952
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Development of a nonhuman primate challenge model to evaluate CD8

    Graveline, Richard / Haida, Morad / Dumont, Carolyne / Poulin, Dominic / Poitout-Belissent, Florence / Samadfam, Rana / Kronenberg, Sven / Regenass-Lechner, Franziska / Prell, Rodney / Piche, Marie-Soleil

    mAbs

    2021  Volume 14, Issue 1, Page(s) 1979447

    Abstract: Targeting immune checkpoint receptors expressed in the T cell synapse induces active and long-lasting antitumor immunity in preclinical tumor models and oncology patients. However, traditional nonhuman primate (NHP) studies in healthy animals have thus ... ...

    Abstract Targeting immune checkpoint receptors expressed in the T cell synapse induces active and long-lasting antitumor immunity in preclinical tumor models and oncology patients. However, traditional nonhuman primate (NHP) studies in healthy animals have thus far demonstrated little to no pharmacological activity or toxicity for checkpoint inhibitors (CPIs), likely due to a quiescent immune system. We developed a NHP vaccine challenge model in Mauritius cynomolgus monkey (MCMs) that elicits a strong CD8
    MeSH term(s) Adenoviridae ; Animals ; CD8-Positive T-Lymphocytes/immunology ; Drug Evaluation ; Macaca fascicularis ; Male ; SAIDS Vaccines/genetics ; SAIDS Vaccines/immunology ; SAIDS Vaccines/pharmacology ; Simian Acquired Immunodeficiency Syndrome/genetics ; Simian Acquired Immunodeficiency Syndrome/immunology ; Simian Acquired Immunodeficiency Syndrome/prevention & control ; Simian Immunodeficiency Virus/genetics ; Simian Immunodeficiency Virus/immunology
    Chemical Substances SAIDS Vaccines
    Language English
    Publishing date 2021-12-16
    Publishing country United States
    Document type Journal Article ; Video-Audio Media
    ZDB-ID 2537838-7
    ISSN 1942-0870 ; 1942-0870
    ISSN (online) 1942-0870
    ISSN 1942-0870
    DOI 10.1080/19420862.2021.1979447
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Current nonclinical approaches for immune assessments of immuno-oncology biotherapeutics.

    Grimaldi, Christine / Ibraghimov, Alex / Kiessling, Andrea / Rattel, Benno / Ji, Changhua / Fuller, Claudette L / Brennan, Frank R / Regenass-Lechner, Franziska / Shenton, Jacintha / Price, Karen D / Piché, Marie-Soleil / Steeves, Meredith A / Prell, Rodney / Dudal, Sherri / Kronenberg, Sven / Freebern, Wendy / Blanset, Diann

    Drug discovery today

    2022  Volume 28, Issue 2, Page(s) 103440

    Abstract: Harnessing the immune system to kill tumors has been revolutionary and, as a result, has had an enormous benefit for patients in extending life and resulting in effective cures in some. However, activation of the immune system can come at the cost of ... ...

    Abstract Harnessing the immune system to kill tumors has been revolutionary and, as a result, has had an enormous benefit for patients in extending life and resulting in effective cures in some. However, activation of the immune system can come at the cost of undesirable adverse events such as cytokine release syndrome, immune-related adverse events, on-target/off-tumor toxicity, neurotoxicity and tumor lysis syndrome, which are safety risks that can be challenging to assess non-clinically. This article provides a review of the biology and mechanisms that can result in immune-mediated adverse effects and describes industry approaches using in vitro and in vivo models to aid in the nonclinical safety risk assessments for immune-oncology modalities. Challenges and limitations of knowledge and models are also discussed.
    MeSH term(s) Humans ; Neoplasms/drug therapy ; Drug-Related Side Effects and Adverse Reactions ; Risk Assessment
    Language English
    Publishing date 2022-11-12
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 1324988-5
    ISSN 1878-5832 ; 1359-6446
    ISSN (online) 1878-5832
    ISSN 1359-6446
    DOI 10.1016/j.drudis.2022.103440
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Recommendations for Method Development and Validation of qPCR and dPCR Assays in Support of Cell and Gene Therapy Drug Development.

    Hays, Amanda / Wissel, Mark / Colletti, Kelly / Soon, Russell / Azadeh, Mitra / Smith, Justin / Doddareddy, Rajitha / Chalfant, Melanie / Adamowicz, Wendy / Ramaswamy, Swarna Suba / Dholakiya, Sanjay L / Guelman, Sebastian / Gullick, Bryan / Durham, Jennifer / Rennier, Keith / Nagilla, Pruthvi / Muruganandham, Anamica / Diaz, Manisha / Tierney, Cassandra /
    John, Kaarthik / Valentine, Jenny / Lockman, Timothy / Liu, Hsing-Yin / Moritz, Benjamin / Ouedraogo, Jean Paul / Piche, Marie-Soleil / Smet, Muriel / Murphy, Jacqueline / Koenig, Kaylyn / Zybura, Agnes / Vyhlidal, Carrie / Mercier, Jonathan / Jani, Niketa / Kubista, Mikael / Birch, Donald / Morse, Karlin / Johansson, Oskar

    The AAPS journal

    2024  Volume 26, Issue 1, Page(s) 24

    Abstract: The emerging use of qPCR and dPCR in regulated bioanalysis and absence of regulatory guidance on assay validations for these platforms has resulted in discussions on lack of harmonization on assay design and appropriate acceptance criteria for these ... ...

    Abstract The emerging use of qPCR and dPCR in regulated bioanalysis and absence of regulatory guidance on assay validations for these platforms has resulted in discussions on lack of harmonization on assay design and appropriate acceptance criteria for these assays. Both qPCR and dPCR are extensively used to answer bioanalytical questions for novel modalities such as cell and gene therapies. Following cross-industry conversations on the lack of information and guidelines for these assays, an American Association of Pharmaceutical Scientists working group was formed to address these gaps by bringing together 37 industry experts from 24 organizations to discuss best practices to gain a better understanding in the industry and facilitate filings to health authorities. Herein, this team provides considerations on assay design, development, and validation testing for PCR assays that are used in cell and gene therapies including (1) biodistribution; (2) transgene expression; (3) viral shedding; (4) and persistence or cellular kinetics of cell therapies.
    MeSH term(s) Tissue Distribution ; Drug Development ; Genetic Therapy ; Polymerase Chain Reaction
    Language English
    Publishing date 2024-02-05
    Publishing country United States
    Document type Journal Article
    ISSN 1550-7416
    ISSN (online) 1550-7416
    DOI 10.1208/s12248-023-00880-9
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Current Practices and Challenges in Method Validation.

    Poitout, Florence / Colangelo, Jennifer L / Lavallée, Simon / Aulbach, Adam D / Piché, Marie-Soleil / Ennulat, Daniela / Ameri, Mehrdad / Boone, Laura I

    Toxicologic pathology

    2018  Volume 46, Issue 7, Page(s) 847–856

    Abstract: Method validation is a cornerstone on which biomarker development and utilization rest. However, given the abundance of biomarker candidates that are being identified and characterized, validation of these entities for the use in nonclinical studies can ... ...

    Abstract Method validation is a cornerstone on which biomarker development and utilization rest. However, given the abundance of biomarker candidates that are being identified and characterized, validation of these entities for the use in nonclinical studies can be complex. The objective of this continuing education course was to review current practices and challenges encountered during the validation of methods for the analysis of novel biomarkers. Additionally, the importance of biological validation and correlation with pathology end points for biomarker candidates was discussed. This article is a summary of the materials presented at the 36th Annual Symposium of the Society of Toxicologic Pathology for a continuing education course titled "Current Practices and Challenges in Method Validation." The speakers were subject-matter experts in the validation of quantitative mass spectrometry, multiplex binding assays, biological biomarkers, and immunophenotyping and anatomic and clinical pathology considerations in biomarker qualification.
    MeSH term(s) Animals ; Biological Assay/methods ; Biological Assay/standards ; Biomarkers/analysis ; Congresses as Topic ; Humans ; Mass Spectrometry/methods ; Mass Spectrometry/standards ; Pathology, Clinical/standards ; Reference Standards ; Reproducibility of Results ; Research Design ; Sensitivity and Specificity ; Toxicity Tests/standards
    Chemical Substances Biomarkers
    Language English
    Publishing date 2018-09-25
    Publishing country United States
    Document type Journal Article
    ZDB-ID 841009-4
    ISSN 1533-1601 ; 0192-6233
    ISSN (online) 1533-1601
    ISSN 0192-6233
    DOI 10.1177/0192623318801571
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Cytokine release: A workshop proceedings on the state-of-the-science, current challenges and future directions.

    Grimaldi, Christine / Finco, Deborah / Fort, Madeline M / Gliddon, Daniel / Harper, Kirsty / Helms, Whitney S / Mitchell, Jane A / O'Lone, Raegan / Parish, Stanley T / Piche, Marie-Soleil / Reed, Daniel M / Reichmann, Gabriele / Ryan, Patricia C / Stebbings, Richard / Walker, Mindi

    Cytokine

    2016  Volume 85, Page(s) 101–108

    Abstract: In October 2013, the International Life Sciences Institute - Health and Environmental Sciences Institute Immunotoxicology Technical Committee (ILSI-HESI ITC) held a one-day workshop entitled, "Workshop on Cytokine Release: State-of-the-Science, Current ... ...

    Abstract In October 2013, the International Life Sciences Institute - Health and Environmental Sciences Institute Immunotoxicology Technical Committee (ILSI-HESI ITC) held a one-day workshop entitled, "Workshop on Cytokine Release: State-of-the-Science, Current Challenges and Future Directions". The workshop brought together scientists from pharmaceutical, academic, health authority, and contract research organizations to discuss novel approaches and current challenges for the use of in vitro cytokine release assays (CRAs) for the identification of cytokine release syndrome (CRS) potential of novel monoclonal antibody (mAb) therapeutics. Topics presented encompassed a regulatory perspective on cytokine release and assessment, case studies regarding the translatability of preclinical cytokine data to the clinic, and the latest state of the science of CRAs, including comparisons between mAb therapeutics within one platform and across several assay platforms, a novel physiological assay platform, and assay optimization approaches such as determination of FcR expression profiles and use of statistical tests. The data and approaches presented confirmed that multiple CRA platforms are in use for identification of CRS potential and that the choice of a particular CRA platform is highly dependent on the availability of resources for individual laboratories (e.g. positive and negative controls, number of human blood donors), the assay through-put required, and the mechanism-of-action of the therapeutic candidate to be tested. Workshop participants agreed that more data on the predictive performance of CRA platforms is needed, and current efforts to compare in vitro assay results with clinical cytokine assessments were discussed. In summary, many laboratories continue to focus research efforts on the improvement of the translatability of current CRA platforms as well explore novel approaches which may lead to more accurate, and potentially patient-specific, CRS prediction in the future.
    Language English
    Publishing date 2016
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1018055-2
    ISSN 1096-0023 ; 1043-4666
    ISSN (online) 1096-0023
    ISSN 1043-4666
    DOI 10.1016/j.cyto.2016.06.006
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: The T-cell-dependent antibody response assay in nonclinical studies of pharmaceuticals and chemicals: study design, data analysis, interpretation.

    Lebrec, Hervé / Molinier, Brigitte / Boverhof, Darrell / Collinge, Mark / Freebern, Wendy / Henson, Kristin / Mytych, Daniel T / Ochs, Hans D / Wange, Ronald / Yang, Yung / Zhou, Lei / Arrington, Joshua / Christin-Piché, Marie Soleil / Shenton, Jacintha

    Regulatory toxicology and pharmacology : RTP

    2014  Volume 69, Issue 1, Page(s) 7–21

    Abstract: The T-cell-dependent antibody response (TDAR) assay is a measure of immune function that is dependent upon the effectiveness of multiple immune processes, including antigen uptake and presentation, T cell help, B cell activation, and antibody production. ...

    Abstract The T-cell-dependent antibody response (TDAR) assay is a measure of immune function that is dependent upon the effectiveness of multiple immune processes, including antigen uptake and presentation, T cell help, B cell activation, and antibody production. It is used for risk and safety assessments, in conjunction with other toxicologic assessments, by the chemical and pharmaceutical industries, and research and regulatory agencies. It is also employed to evaluate investigational drug efficacy in animal pharmacology studies, provide evidence of biological impact in clinical trials, and evaluate immune function in patients with primary or secondary immunodeficiency diseases. Various immunization schemes, analytical methods, approaches to data analysis, and data interpretations are in use. This manuscript summarizes some recommended practices for the conduct and interpretation of the assay in animal studies.
    MeSH term(s) Animals ; Antibody Formation/immunology ; Biological Assay/methods ; Clinical Trials as Topic ; Drug Industry/methods ; Humans ; Research Design ; Risk Assessment/methods ; T-Lymphocytes/immunology
    Language English
    Publishing date 2014-06
    Publishing country Netherlands
    Document type Journal Article ; Review
    ZDB-ID 604672-1
    ISSN 1096-0295 ; 0273-2300
    ISSN (online) 1096-0295
    ISSN 0273-2300
    DOI 10.1016/j.yrtph.2014.02.008
    Database MEDical Literature Analysis and Retrieval System OnLINE

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