TY - JOUR
T1 - Current and potential roles of immuno-PET/-SPECT in CAR T-cell therapy
AU - Mulgaonkar, Aditi
AU - Udayakumar, Durga
AU - Yang, Yaxing
AU - Harris, Shelby
AU - Öz, Orhan K.
AU - Ramakrishnan Geethakumari, Praveen
AU - Sun, Xiankai
N1 - Publisher Copyright:
Copyright © 2023 Mulgaonkar, Udayakumar, Yang, Harris, Öz, Ramakrishnan Geethakumari and Sun.
PY - 2023
Y1 - 2023
N2 - Chimeric antigen receptor (CAR) T-cell therapies have evolved as breakthrough treatment options for the management of hematological malignancies and are also being developed as therapeutics for solid tumors. However, despite the impressive patient responses from CD19-directed CAR T-cell therapies, ~ 40%−60% of these patients' cancers eventually relapse, with variable prognosis. Such relapses may occur due to a combination of molecular resistance mechanisms, including antigen loss or mutations, T-cell exhaustion, and progression of the immunosuppressive tumor microenvironment. This class of therapeutics is also associated with certain unique toxicities, such as cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome, and other “on-target, off-tumor” toxicities, as well as anaphylactic effects. Furthermore, manufacturing limitations and challenges associated with solid tumor infiltration have delayed extensive applications. The molecular imaging modalities of immunological positron emission tomography and single-photon emission computed tomography (immuno-PET/-SPECT) offer a target-specific and highly sensitive, quantitative, non-invasive platform for longitudinal detection of dynamic variations in target antigen expression in the body. Leveraging these imaging strategies as guidance tools for use with CAR T-cell therapies may enable the timely identification of resistance mechanisms and/or toxic events when they occur, permitting effective therapeutic interventions. In addition, the utilization of these approaches in tracking the CAR T-cell pharmacokinetics during product development and optimization may help to assess their efficacy and accordingly to predict treatment outcomes. In this review, we focus on current challenges and potential opportunities in the application of immuno-PET/-SPECT imaging strategies to address the challenges encountered with CAR T-cell therapies.
AB - Chimeric antigen receptor (CAR) T-cell therapies have evolved as breakthrough treatment options for the management of hematological malignancies and are also being developed as therapeutics for solid tumors. However, despite the impressive patient responses from CD19-directed CAR T-cell therapies, ~ 40%−60% of these patients' cancers eventually relapse, with variable prognosis. Such relapses may occur due to a combination of molecular resistance mechanisms, including antigen loss or mutations, T-cell exhaustion, and progression of the immunosuppressive tumor microenvironment. This class of therapeutics is also associated with certain unique toxicities, such as cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome, and other “on-target, off-tumor” toxicities, as well as anaphylactic effects. Furthermore, manufacturing limitations and challenges associated with solid tumor infiltration have delayed extensive applications. The molecular imaging modalities of immunological positron emission tomography and single-photon emission computed tomography (immuno-PET/-SPECT) offer a target-specific and highly sensitive, quantitative, non-invasive platform for longitudinal detection of dynamic variations in target antigen expression in the body. Leveraging these imaging strategies as guidance tools for use with CAR T-cell therapies may enable the timely identification of resistance mechanisms and/or toxic events when they occur, permitting effective therapeutic interventions. In addition, the utilization of these approaches in tracking the CAR T-cell pharmacokinetics during product development and optimization may help to assess their efficacy and accordingly to predict treatment outcomes. In this review, we focus on current challenges and potential opportunities in the application of immuno-PET/-SPECT imaging strategies to address the challenges encountered with CAR T-cell therapies.
KW - CAR T-cell therapy
KW - cell therapy
KW - immuno-PET
KW - immuno-SPECT
KW - tumor microenvironment
UR - http://www.scopus.com/inward/record.url?scp=85164725015&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85164725015&partnerID=8YFLogxK
U2 - 10.3389/fmed.2023.1199146
DO - 10.3389/fmed.2023.1199146
M3 - Review article
C2 - 37441689
AN - SCOPUS:85164725015
SN - 2296-858X
VL - 10
JO - Frontiers in Medicine
JF - Frontiers in Medicine
M1 - 1199146
ER -