Autologous engineered T cell receptor therapy in advanced cancer

ABSTRACTTo overcome challenges associated with adoptive cell therapy (ACT), we developed a personalized autologous T-cell therapy program. Patients with advanced cancer with HLA-A *02:01 allele and tumor expression of PRAME, MAGEA1, MAGEA4, MAGEA8, NY-ESO-1, COL6A3 exon 6, MXRA5, and/or MMP1 underwe...

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Main Authors: Apostolia M. Tsimberidou, Mehmet A. Baysal, Abhijit Chakraborty, Borje S. Andersson
Format: Article
Language:English
Published: Taylor & Francis Group 2023-12-01
Series:Human Vaccines & Immunotherapeutics
Subjects:
Online Access:https://www.tandfonline.com/doi/10.1080/21645515.2023.2290356
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author Apostolia M. Tsimberidou
Mehmet A. Baysal
Abhijit Chakraborty
Borje S. Andersson
author_facet Apostolia M. Tsimberidou
Mehmet A. Baysal
Abhijit Chakraborty
Borje S. Andersson
author_sort Apostolia M. Tsimberidou
collection DOAJ
description ABSTRACTTo overcome challenges associated with adoptive cell therapy (ACT), we developed a personalized autologous T-cell therapy program. Patients with advanced cancer with HLA-A *02:01 allele and tumor expression of PRAME, MAGEA1, MAGEA4, MAGEA8, NY-ESO-1, COL6A3 exon 6, MXRA5, and/or MMP1 underwent leukapheresis and T-cell product manufacturing. Patients received lymphodepletion, IMA101 infusion and interleukin 2 for 14 days. Of 214 screened patients, 14 were treated (6, IMA101; 8, IMA101 and atezolizumab). The most common adverse events were cytokine release syndrome (G1, n = 6; G2, n = 4) and cytopenia. At 6 weeks, 12 (85.7%) patients had stable disease. Three patients had prolonged disease stabilization for 12.9, 7.3, and 13.7 months, respectively. The median progression-free survival and overall survival were 3.4 months and 9.4 months, respectively. Target-specific T cells expanded to constitute up to 78.7% of CD8+ cells. In conclusion, IMA101 was feasible and well tolerated, leveraging the potential of multi-targeted ACT that warrants further investigation.
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spelling doaj.art-feb043363ffc49cca62e71ac4fff02e92024-01-19T13:34:13ZengTaylor & Francis GroupHuman Vaccines & Immunotherapeutics2164-55152164-554X2023-12-0119310.1080/21645515.2023.2290356Autologous engineered T cell receptor therapy in advanced cancerApostolia M. Tsimberidou0Mehmet A. Baysal1Abhijit Chakraborty2Borje S. Andersson3Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, USADepartment of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, USADepartment of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, USADepartment of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX, USAABSTRACTTo overcome challenges associated with adoptive cell therapy (ACT), we developed a personalized autologous T-cell therapy program. Patients with advanced cancer with HLA-A *02:01 allele and tumor expression of PRAME, MAGEA1, MAGEA4, MAGEA8, NY-ESO-1, COL6A3 exon 6, MXRA5, and/or MMP1 underwent leukapheresis and T-cell product manufacturing. Patients received lymphodepletion, IMA101 infusion and interleukin 2 for 14 days. Of 214 screened patients, 14 were treated (6, IMA101; 8, IMA101 and atezolizumab). The most common adverse events were cytokine release syndrome (G1, n = 6; G2, n = 4) and cytopenia. At 6 weeks, 12 (85.7%) patients had stable disease. Three patients had prolonged disease stabilization for 12.9, 7.3, and 13.7 months, respectively. The median progression-free survival and overall survival were 3.4 months and 9.4 months, respectively. Target-specific T cells expanded to constitute up to 78.7% of CD8+ cells. In conclusion, IMA101 was feasible and well tolerated, leveraging the potential of multi-targeted ACT that warrants further investigation.https://www.tandfonline.com/doi/10.1080/21645515.2023.2290356Multitargeted autologous T-cell therapylymphodepletionadvanced canceradoptive cell therapyACTT- cell nfusion
spellingShingle Apostolia M. Tsimberidou
Mehmet A. Baysal
Abhijit Chakraborty
Borje S. Andersson
Autologous engineered T cell receptor therapy in advanced cancer
Human Vaccines & Immunotherapeutics
Multitargeted autologous T-cell therapy
lymphodepletion
advanced cancer
adoptive cell therapy
ACT
T- cell nfusion
title Autologous engineered T cell receptor therapy in advanced cancer
title_full Autologous engineered T cell receptor therapy in advanced cancer
title_fullStr Autologous engineered T cell receptor therapy in advanced cancer
title_full_unstemmed Autologous engineered T cell receptor therapy in advanced cancer
title_short Autologous engineered T cell receptor therapy in advanced cancer
title_sort autologous engineered t cell receptor therapy in advanced cancer
topic Multitargeted autologous T-cell therapy
lymphodepletion
advanced cancer
adoptive cell therapy
ACT
T- cell nfusion
url https://www.tandfonline.com/doi/10.1080/21645515.2023.2290356
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AT mehmetabaysal autologousengineeredtcellreceptortherapyinadvancedcancer
AT abhijitchakraborty autologousengineeredtcellreceptortherapyinadvancedcancer
AT borjesandersson autologousengineeredtcellreceptortherapyinadvancedcancer