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Genetic Modification of Cytokine Signaling to Enhance Efficacy of Car T Cell Therapy in Solid Tumors Publisher Pubmed



Ghahrisaremi N1 ; Akbari B1 ; Soltantoyeh T1 ; Hadjati J1 ; Ghassemi S2 ; Mirzaei HR1
Authors

Source: Frontiers in Immunology Published:2021


Abstract

Chimeric antigen receptor (CAR) T cell therapy has shown unprecedented success in treating advanced hematological malignancies. Its effectiveness in solid tumors has been limited due to heterogeneous antigen expression, a suppressive tumor microenvironment, suboptimal trafficking to the tumor site and poor CAR T cell persistence. Several approaches have been developed to overcome these obstacles through various strategies including the genetic engineering of CAR T cells to blunt the signaling of immune inhibitory receptors as well as to modulate signaling of cytokine/chemokine molecules and their receptors. In this review we offer our perspective on how genetically modifying cytokine/chemokine molecules and their receptors can improve CAR T cell qualities such as functionality, persistence (e.g. resistance to pro-apoptotic signals) and infiltration into tumor sites. Understanding how such modifications can overcome barriers to CAR T cell effectiveness will undoubtedly enhance the potential of CAR T cells against solid tumors. © Copyright © 2021 Ghahri-Saremi, Akbari, Soltantoyeh, Hadjati, Ghassemi and Mirzaei.
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