An Overview of Cytokine Release Syndrome and Other Side Effects of CAR-T                Cell Therapy

Genoud, Vassilis; Migliorini, Denis

doi:10.1024/1661-8157/a003980

Cited by 3 publications

(4 citation statements)

References 23 publications

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“…However, rapid progression to hemodynamic instability, respiratory failure, organ dysfunction, shock, and hemophagocytic lymphohistiocytosis has also been reported. 74 CRS typically occurs within 1-2 weeks of CAR T-cell infusion depending on the product but can occur as early as a few hours post-infusion. 75 CRS has a reported incidence between 37% and 93% across different studies.…”

Section: Non-infectious Complications Of Car T-cell Therapymentioning

confidence: 99%

“…84 Inflammatory cytokines released by macrophages, specifically IL-6 and IL-1, have been widely identified as critical components in the pathogenesis of CRS and ICANS, respectively. 74,85 Elevated serum levels of IL-6 are one of the most correlated findings with CRS. Activated CAR T cells release IFN-γ, TNF-α, and granulocyte-macrophage colony stimulating factor (GM-CSF) to induce tumor cell cytolysis.…”

Section: Car T Productmentioning

confidence: 99%

“…87 Tocilizumab, a monoclonal IL-6 receptor (IL-6R) blocking antibody, is used to treat CRS. 74 Interestingly, IL-6R blockade has not been shown to be effective in the treatment of ICANS. However, IL-1 receptor blockade has been shown to improve ICANS.…”

Section: Car T Productmentioning

confidence: 99%

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The shifting roles and toxicities of cellular therapies in B‐cell malignancies

Makos,

D'Angelo

2023

Transplant Infectious Dis

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Cellular therapies provide a curative‐intent option for patients with relapsedand refractory lymphomas. Current options including high dose chemotherapyfollowed by autologous or allogeneic hematopoietic stem cell transplantation or CD19 chimericantigen receptor T‐cell (CART) therapy. The indication varies according to lymphoma sub‐type and line oftherapy. The sequencing of these therapies and their use in second‐line orlater settings to manage these diseases is undergoing significant changes, withCD19 CAR T becoming a preferred option for relapsed aggressive B‐cell lymphoma.The mechanism of both therapies causes significant yet distinctlymphodepletion, infectious, and inflammatory toxicities. The resulting patternand timing of immune reconstitution helps guide risk‐mitigating strategies,revaccination, and infectious prophylaxis. In this review, we discuss theindication, efficacy, toxicity and immune reconstitution of autologoushematopoietic stem cell transplantation and CAR T therapy for use in thetreatment of lymphoma.

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Section: Non-infectious Complications Of Car T-cell Therapymentioning

confidence: 99%

Section: Car T Productmentioning

confidence: 99%

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The shifting roles and toxicities of cellular therapies in B‐cell malignancies

Makos,

D'Angelo

2023

Transplant Infectious Dis

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“…Efficacy of currently available bsAbs and CAR T cells is additionally hampered by side effects due to unspecific activation of the T cells, resulting in a potentially lethal cytokine release syndrome (CRS) ( 23 , 24 ). This is due to the employed target antigens frequently being not exclusively expressed not only on malignant but also on healthy cells.…”

Section: Introductionmentioning

confidence: 99%

Protocol of a first-in-human clinical trial to evaluate the safety, tolerability, and preliminary efficacy of the bispecific CD276xCD3 antibody CC-3 in patients with colorectal cancer (CoRe_CC-3)

Jung,

Schlenk,

Hackenbruch

et al. 2024

Front. Oncol.

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IntroductionColorectal cancer (CRC) is the third most common cancer worldwide in men and women. In the metastasized stage, treatment options and prognosis are limited. To address the high medical need of this patient population, we generated a CD276xCD3 bispecific antibody termed CC-3. CD276 is expressed on CRC cells and on tumor vessels, thereby allowing for a “dual” anticancer effect.Methods and analysisThis first-in-human clinical study is planned as a prospective multicenter trial, enrolling patients with metastatic CRC after three lines of therapy. During the dose-escalation part, initially, an accelerated titration design with single-patient cohorts is employed. Here, each patient will receive a fixed dose level (starting with 50 µg for the first patient); however, between patients, dose level may be increased by up to 100%, depending on the decision of a safety review committee. Upon occurrence of any adverse events (AEs) grade ≥2, dose-limiting toxicity (DLT), or reaching a dose level of ≥800 µg, the escalation will switch to a standard 3 + 3 dose design. After maximum tolerated dose (MTD) has been determined, defined as no more than one of the six patients experiencing DLT, an additional 14 patients receive CC-3 at the MTD level in the dose-expansion phase. Primary endpoints are incidence and severity of AEs, as well as the best objective response to the treatment according to response evaluation criteria in solid tumors (RECIST) 1.1. Secondary endpoints include overall safety, efficacy, survival, quality of life, and pharmacokinetic investigations.Ethics and disseminationThe CD276xCD3 study was approved by the Ethics Committee of the Medical Faculty of the Heinrich Heine University Düsseldorf and the Paul-Ehrlich-Institut (P00702). Clinical trial results will be published in peer-reviewed journals. Trial registration numbers: ClinicalTrials.cov Registry (NCT05999396) and EU ClinicalTrials Registry (EU trial number 2022-503084-15-00).

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Cancer Immunotherapy: One Century to Shift from a Crazy Hypothesis to Daily Practice

Dietrich

2023

Praxis

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An Overview of Cytokine Release Syndrome and Other Side Effects of CAR-T Cell Therapy

Cited by 3 publications

References 23 publications

The shifting roles and toxicities of cellular therapies in B‐cell malignancies

The shifting roles and toxicities of cellular therapies in B‐cell malignancies

Protocol of a first-in-human clinical trial to evaluate the safety, tolerability, and preliminary efficacy of the bispecific CD276xCD3 antibody CC-3 in patients with colorectal cancer (CoRe_CC-3)

Cancer Immunotherapy: One Century to Shift from a Crazy Hypothesis to Daily Practice

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