TY - JOUR
T1 - A novel method to generate and expand clinical-grade, genetically modified, tumor-infiltrating lymphocytes
AU - Forget, Marie Andrée
AU - Tavera, René J.
AU - Haymaker, Cara
AU - Ramachandran, Renjith
AU - Malu, Shuti
AU - Zhang, Minying
AU - Wardell, Seth
AU - Fulbright, Orenthial J.
AU - Toth, Chistopher Leroy
AU - Gonzalez, Audrey M.
AU - Thorsen, Shawne T.
AU - Flores, Esteban
AU - Wahl, Arely
AU - Peng, Weiyi
AU - Amaria, Rodabe N.
AU - Hwu, Patrick
AU - Bernatchez, Chantale
N1 - Publisher Copyright:
© 2017 Forget, Tavera, Haymaker, Ramachandran, Malu, Zhang, Wardell, Fulbright, Toth, Gonzalez, Thorsen, Flores, Wahl, Peng, Amaria, Hwu and Bernatchez.
PY - 2017/8/2
Y1 - 2017/8/2
N2 - Following the clinical success achieved with the first generation of adoptive cell therapy (ACT) utilizing in vitro expanded tumor-infiltrating lymphocytes (TILs), the second and third generations of TIL ACT are evolving toward the use of genetically modified TIL. TIL therapy generally involves the transfer of a high number of TIL, ranging from 109 to 1011 cells. One of the technical difficulties in genetically modifying TIL, using a retroviral vector, is the ability to achieve large expansion of transduced TIL, while keeping the technique suitable to a Good Manufacturing Practices (GMP) environment. Consequently, we developed and optimized a novel method for the efficient production of large numbers of GMP-grade, gene-modified TIL for the treatment of patients with ACT. The chemokine receptor CXCR2 was used as the gene of interest for methodology development. The optimized procedure is currently used in the production of gene-modified TIL for two clinical trials for the treatment of metastatic melanoma at MD Anderson Cancer Center.
AB - Following the clinical success achieved with the first generation of adoptive cell therapy (ACT) utilizing in vitro expanded tumor-infiltrating lymphocytes (TILs), the second and third generations of TIL ACT are evolving toward the use of genetically modified TIL. TIL therapy generally involves the transfer of a high number of TIL, ranging from 109 to 1011 cells. One of the technical difficulties in genetically modifying TIL, using a retroviral vector, is the ability to achieve large expansion of transduced TIL, while keeping the technique suitable to a Good Manufacturing Practices (GMP) environment. Consequently, we developed and optimized a novel method for the efficient production of large numbers of GMP-grade, gene-modified TIL for the treatment of patients with ACT. The chemokine receptor CXCR2 was used as the gene of interest for methodology development. The optimized procedure is currently used in the production of gene-modified TIL for two clinical trials for the treatment of metastatic melanoma at MD Anderson Cancer Center.
KW - Adoptive cell therapy
KW - Clinical-grade
KW - Genetic modification
KW - Good Manufacturing Practice
KW - Retroviral-transduction
KW - Tumor-infiltrating lymphocytes
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U2 - 10.3389/fimmu.2017.00908
DO - 10.3389/fimmu.2017.00908
M3 - Article
C2 - 28824634
AN - SCOPUS:85026727528
SN - 1664-3224
VL - 8
JO - Frontiers in immunology
JF - Frontiers in immunology
IS - AUG
M1 - 908
ER -