TY - JOUR
T1 - Autologous engineered T cell receptor therapy in advanced cancer
AU - Tsimberidou, Apostolia M.
AU - Baysal, Mehmet A.
AU - Chakraborty, Abhijit
AU - Andersson, Borje S
N1 - Publisher Copyright:
© 2023 The Author(s). Published with license by Taylor & Francis Group, LLC.
PY - 2023
Y1 - 2023
N2 - To 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.
AB - To 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.
KW - ACT
KW - adoptive cell therapy
KW - advanced cancer
KW - atezolizumab
KW - lymphodepletion
KW - Multitargeted autologous T-cell therapy
KW - T- cell nfusion
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U2 - 10.1080/21645515.2023.2290356
DO - 10.1080/21645515.2023.2290356
M3 - Review article
C2 - 38114231
AN - SCOPUS:85180419805
SN - 2164-5515
VL - 19
JO - Human Vaccines and Immunotherapeutics
JF - Human Vaccines and Immunotherapeutics
IS - 3
M1 - 2290356
ER -