Controlling Cytokine Release Syndrome to Harness the Full Potential of CAR-Based Cellular Therapy
Identifieur interne : 000474 ( Main/Exploration ); précédent : 000473; suivant : 000475Controlling Cytokine Release Syndrome to Harness the Full Potential of CAR-Based Cellular Therapy
Auteurs : Monica S. Thakar [États-Unis] ; Tyce J. Kearl [États-Unis] ; Subramaniam Malarkannan [États-Unis]Source :
- Frontiers in Oncology [ 2234-943X ] ; 2020.
Abstract
Chimeric Antigen Receptor (CAR)-based therapies offer a promising, targeted approach to effectively treat relapsed or refractory B cell malignancies. However, the treatment-related toxicity defined as cytokine-release syndrome (CRS) often develops in patients, and if uncontrolled, can be fatal. Grading systems have now been developed to further characterize and objectify clinical findings in order to provide algorithm-based guidance on CRS-related treatment decisions. The pharmacological treatments associated with these algorithms suppress inflammation through a variety of mechanisms and are paramount to improving the safety profile of CAR-based therapies. However, fatalities are still occurring, and there are downsides to these treatments, including the possibility of disrupting CAR-T cell persistence. This review article will describe the clinical presentation and current management of CRS, and through our now deeper understanding of downstream signaling pathways, will provide a molecular framework to formulate new hypotheses regarding clinical applications to contain proinflammatory cytokines responsible for CRS.
Url:
DOI: 10.3389/fonc.2019.01529
PubMed: 32076597
PubMed Central: 7006459
Affiliations:
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Kearl</name><affiliation wicri:level="1"><nlm:aff id="aff1"><institution>Laboratory of Molecular Immunology and Immunotherapy, Blood Research Institute, Versiti</institution>,<addr-line>Milwaukee, WI</addr-line>,<country>United States</country></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff2"><institution>Department of Pediatrics, Medical College of Wisconsin</institution>,<addr-line>Milwaukee, WI</addr-line>,<country>United States</country></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Malarkannan, Subramaniam" sort="Malarkannan, Subramaniam" uniqKey="Malarkannan S" first="Subramaniam" last="Malarkannan">Subramaniam Malarkannan</name><affiliation wicri:level="1"><nlm:aff id="aff1"><institution>Laboratory of Molecular Immunology and Immunotherapy, Blood Research Institute, Versiti</institution>,<addr-line>Milwaukee, WI</addr-line>,<country>United States</country></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff2"><institution>Department of Pediatrics, Medical College of Wisconsin</institution>,<addr-line>Milwaukee, WI</addr-line>,<country>United States</country></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff3"><institution>Department of Medicine, Medical College of Wisconsin</institution>,<addr-line>Milwaukee, WI</addr-line>,<country>United States</country></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff4"><institution>Department of Microbiology and Immunology, Medical College of Wisconsin</institution>,<addr-line>Milwaukee, WI</addr-line>,<country>United States</country></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff5"><institution>Center of Excellence in Prostate Cancer, Medical College of Wisconsin</institution>,<addr-line>Milwaukee, WI</addr-line>,<country>United States</country></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author></analytic><series><title level="j">Frontiers in Oncology</title><idno type="eISSN">2234-943X</idno><imprint><date when="2020">2020</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Chimeric Antigen Receptor (CAR)-based therapies offer a promising, targeted approach to effectively treat relapsed or refractory B cell malignancies. However, the treatment-related toxicity defined as cytokine-release syndrome (CRS) often develops in patients, and if uncontrolled, can be fatal. Grading systems have now been developed to further characterize and objectify clinical findings in order to provide algorithm-based guidance on CRS-related treatment decisions. The pharmacological treatments associated with these algorithms suppress inflammation through a variety of mechanisms and are paramount to improving the safety profile of CAR-based therapies. However, fatalities are still occurring, and there are downsides to these treatments, including the possibility of disrupting CAR-T cell persistence. This review article will describe the clinical presentation and current management of CRS, and through our now deeper understanding of downstream signaling pathways, will provide a molecular framework to formulate new hypotheses regarding clinical applications to contain proinflammatory cytokines responsible for CRS.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Teras, Lr" uniqKey="Teras L">LR Teras</name></author><author><name sortKey="Desantis, Ce" uniqKey="Desantis C">CE DeSantis</name></author><author><name sortKey="Cerhan, Jr" uniqKey="Cerhan J">JR Cerhan</name></author><author><name sortKey="Morton, Lm" uniqKey="Morton L">LM Morton</name></author><author><name sortKey="Jemal, A" uniqKey="Jemal A">A Jemal</name></author><author><name sortKey="Flowers, Cr" uniqKey="Flowers C">CR Flowers</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Crump, M" uniqKey="Crump M">M 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Thakar</name></noRegion><name sortKey="Kearl, Tyce J" sort="Kearl, Tyce J" uniqKey="Kearl T" first="Tyce J." last="Kearl">Tyce J. Kearl</name><name sortKey="Kearl, Tyce J" sort="Kearl, Tyce J" uniqKey="Kearl T" first="Tyce J." last="Kearl">Tyce J. Kearl</name><name sortKey="Malarkannan, Subramaniam" sort="Malarkannan, Subramaniam" uniqKey="Malarkannan S" first="Subramaniam" last="Malarkannan">Subramaniam Malarkannan</name><name sortKey="Malarkannan, Subramaniam" sort="Malarkannan, Subramaniam" uniqKey="Malarkannan S" first="Subramaniam" last="Malarkannan">Subramaniam Malarkannan</name><name sortKey="Malarkannan, Subramaniam" sort="Malarkannan, Subramaniam" uniqKey="Malarkannan S" first="Subramaniam" last="Malarkannan">Subramaniam Malarkannan</name><name sortKey="Malarkannan, Subramaniam" sort="Malarkannan, Subramaniam" uniqKey="Malarkannan S" first="Subramaniam" last="Malarkannan">Subramaniam Malarkannan</name><name sortKey="Malarkannan, Subramaniam" sort="Malarkannan, Subramaniam" uniqKey="Malarkannan S" first="Subramaniam" last="Malarkannan">Subramaniam Malarkannan</name><name sortKey="Thakar, Monica S" sort="Thakar, Monica S" uniqKey="Thakar M" first="Monica S." last="Thakar">Monica S. 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