TY - JOUR
T1 - A Computational Model of Cytokine Release Syndrome during CAR T-Cell Therapy
AU - Zhang, Zhuoyu
AU - Liu, Lunan
AU - Ma, Chao
AU - Chen, Weiqiang
N1 - Funding Information:
This work was supported by the National Science Foundation (CBET2103219), US National Institutes of Health (R35GM133646), and Cancer Research Institute Irvington Postdoctoral Fellowship (CRI4018).
Publisher Copyright:
© 2022 Wiley-VCH GmbH.
PY - 2022/10
Y1 - 2022/10
N2 - Cytokine release syndrome (CRS) is a lethal adverse event in chimeric antigen receptor (CAR) T-cell therapy, hindering this promising therapy for cancers, such as B-cell acute lymphoblastic leukemia (B-ALL). Clinical management of CRS requires a better understanding of its underlying mechanisms. In this study, a computational model of CRS during CAR T-cell therapy is built to depict how the cellular interactions among CAR T-cells, B-ALL cells, and bystander monocytes, as well as the accompanying molecular interactions among various inflammatory cytokines, influence the severity of CRS. The model successfully defines the factors related to severe CRS and studies the effects of immunomodulatory therapy on CRS. The use of the model is also demonstrated as a precision medicine tool to optimize the treatment scheme, including personalized choice of CAR T-cell products and control of switchable CAR T-cell activity, for a more efficient and safer immunotherapy. This new computational oncology model can serve as a precision medicine tool to guide the clinical management of CRS during CAR T cell therapy.
AB - Cytokine release syndrome (CRS) is a lethal adverse event in chimeric antigen receptor (CAR) T-cell therapy, hindering this promising therapy for cancers, such as B-cell acute lymphoblastic leukemia (B-ALL). Clinical management of CRS requires a better understanding of its underlying mechanisms. In this study, a computational model of CRS during CAR T-cell therapy is built to depict how the cellular interactions among CAR T-cells, B-ALL cells, and bystander monocytes, as well as the accompanying molecular interactions among various inflammatory cytokines, influence the severity of CRS. The model successfully defines the factors related to severe CRS and studies the effects of immunomodulatory therapy on CRS. The use of the model is also demonstrated as a precision medicine tool to optimize the treatment scheme, including personalized choice of CAR T-cell products and control of switchable CAR T-cell activity, for a more efficient and safer immunotherapy. This new computational oncology model can serve as a precision medicine tool to guide the clinical management of CRS during CAR T cell therapy.
KW - antigen receptor T-cell therapy
KW - computational model
KW - cytokine release syndrome
KW - leukemia
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U2 - 10.1002/adtp.202200130
DO - 10.1002/adtp.202200130
M3 - Article
AN - SCOPUS:85135800684
SN - 2366-3987
VL - 5
JO - Advanced Therapeutics
JF - Advanced Therapeutics
IS - 10
M1 - 2200130
ER -