Bispecific T-cell engaging therapies harness the immune system to elicit an effective anticancer response. Modulating the immune activation avoiding potential adverse effects such as cytokine release syndrome (CRS) is a critical aspect to realizing the full potential of this therapy. The use of suitable exogenous intervention strategies to mitigate the CRS risk without compromising the antitumoral capability of bispecific antibody treatment is crucial. To this end, computational approaches can be instrumental to systematically exploring the effects of combining bispecific antibodies with CRS intervention strategies. Here, we employ a logical model to describe the action of bispecific antibodies and the complex interplay of various immune system components and use it to perform simulation experiments to improve the understanding of the factors affecting CRS. We performed a sensitivity analysis to identify the comedications that could ameliorate CRS without impairing tumor clearance. Our results agree with publicly available experimental data suggesting anti-TNF and anti-IL6 as possible co-treatments. Furthermore, we suggest anti-IFNγ as a suitable candidate for clinical studies.

Computational Analysis of Cytokine Release Following Bispecific T-Cell Engager Therapy: Applications of a Logic-Based Model / Selvaggio, G.; Parolo, S.; Bora, P.; Leonardelli, L.; Harrold, J.; Mehta, K.; Rock, D. A.; Marchetti, L.. - In: FRONTIERS IN ONCOLOGY. - ISSN 2234-943X. - 12:(2022), pp. 81864101-81864111. [10.3389/fonc.2022.818641]

Computational Analysis of Cytokine Release Following Bispecific T-Cell Engager Therapy: Applications of a Logic-Based Model

Leonardelli L.;Marchetti L.
2022-01-01

Abstract

Bispecific T-cell engaging therapies harness the immune system to elicit an effective anticancer response. Modulating the immune activation avoiding potential adverse effects such as cytokine release syndrome (CRS) is a critical aspect to realizing the full potential of this therapy. The use of suitable exogenous intervention strategies to mitigate the CRS risk without compromising the antitumoral capability of bispecific antibody treatment is crucial. To this end, computational approaches can be instrumental to systematically exploring the effects of combining bispecific antibodies with CRS intervention strategies. Here, we employ a logical model to describe the action of bispecific antibodies and the complex interplay of various immune system components and use it to perform simulation experiments to improve the understanding of the factors affecting CRS. We performed a sensitivity analysis to identify the comedications that could ameliorate CRS without impairing tumor clearance. Our results agree with publicly available experimental data suggesting anti-TNF and anti-IL6 as possible co-treatments. Furthermore, we suggest anti-IFNγ as a suitable candidate for clinical studies.
2022
Selvaggio, G.; Parolo, S.; Bora, P.; Leonardelli, L.; Harrold, J.; Mehta, K.; Rock, D. A.; Marchetti, L.
Computational Analysis of Cytokine Release Following Bispecific T-Cell Engager Therapy: Applications of a Logic-Based Model / Selvaggio, G.; Parolo, S.; Bora, P.; Leonardelli, L.; Harrold, J.; Mehta, K.; Rock, D. A.; Marchetti, L.. - In: FRONTIERS IN ONCOLOGY. - ISSN 2234-943X. - 12:(2022), pp. 81864101-81864111. [10.3389/fonc.2022.818641]
File in questo prodotto:
File Dimensione Formato  
SelvaggioEtAl_BiTE_fonc-12-818641.pdf

accesso aperto

Tipologia: Versione editoriale (Publisher’s layout)
Licenza: Creative commons
Dimensione 3.18 MB
Formato Adobe PDF
3.18 MB Adobe PDF Visualizza/Apri

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11572/341999
Citazioni
  • ???jsp.display-item.citation.pmc??? 0
  • Scopus 3
  • ???jsp.display-item.citation.isi??? 1
social impact