Immune reconstitution and clinical recovery following anti-CD28 antibody (TGN1412)-induced cytokine storm.
Cancer Immunol Immunother
; 70(4): 1127-1142, 2021 Apr.
Article
in English
| MEDLINE | ID: covidwho-841222
ABSTRACT
Cytokine storm can result from cancer immunotherapy or certain infections, including COVID-19. Though short-term immune-related adverse events are routinely described, longer-term immune consequences and sequential immune monitoring are not as well defined. In 2006, six healthy volunteers received TGN1412, a CD28 superagonist antibody, in a first-in-man clinical trial and suffered from cytokine storm. After the initial cytokine release, antibody effect-specific immune monitoring started on Day + 10 and consisted mainly of evaluation of dendritic cell and T-cell subsets and 15 serum cytokines at 21 time-points over 2 years. All patients developed problems with concentration and memory; three patients were diagnosed with mild-to-moderate depression. Mild neutropenia and autoantibody production was observed intermittently. One patient suffered from peripheral dry gangrene, required amputations, and had persistent Raynaud's phenomenon. Gastrointestinal irritability was noted in three patients and coincided with elevated γδT-cells. One had pruritus associated with elevated IgE levels, also found in three other asymptomatic patients. Dendritic cells, initially undetectable, rose to normal within a month. Naïve CD8+ T-cells were maintained at high levels, whereas naïve CD4+ and memory CD4+ and CD8+ T-cells started high but declined over 2 years. T-regulatory cells cycled circannually and were normal in number. Cytokine dysregulation was especially noted in one patient with systemic symptoms. Over a 2-year follow-up, cognitive deficits were observed in all patients following TGN1412 infusion. Some also had signs or symptoms of psychological, mucosal or immune dysregulation. These observations may discern immunopathology, treatment targets, and long-term monitoring strategies for other patients undergoing immunotherapy or with cytokine storm.
Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
T-Lymphocytes
/
CD28 Antigens
/
Drug-Related Side Effects and Adverse Reactions
/
Antibodies, Monoclonal, Humanized
/
Cognitive Dysfunction
/
Cytokine Release Syndrome
/
SARS-CoV-2
/
COVID-19
/
Immunotherapy
Type of study:
Cohort study
/
Experimental Studies
/
Observational study
/
Prognostic study
/
Randomized controlled trials
Topics:
Long Covid
Limits:
Adult
/
Humans
/
Male
/
Young adult
Language:
English
Journal:
Cancer Immunol Immunother
Journal subject:
Allergy and Immunology
/
Neoplasms
/
Therapeutics
Year:
2021
Document Type:
Article
Affiliation country:
S00262-020-02725-2
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