Pre-treatment with systemic agents for advanced NSCLC elicits changes in the phenotype of autologous T cell therapy products

Charlotte O'Brien Gore; Amy Billman; Suchete Hunjan; Jayne Colebrook; Desmond Choy; Wilson Li; Jack Haynes; Jennifer Wade; Emily Hobern; Louisa McDonald; Sophie Papa; Martijn Brugman; Shahram Kordasti; Claudia Montiel-Equihua

doi:10.1016/j.omto.2023.100749

Pre-treatment with systemic agents for advanced NSCLC elicits changes in the phenotype of autologous T cell therapy products

Charlotte O'Brien Gore, Amy Billman, Suchete Hunjan, Jayne Colebrook, Desmond Choy, Wilson Li, Jack Haynes, Jennifer Wade, Emily Hobern, Louisa McDonald, Sophie Papa, Martijn Brugman, Shahram Kordasti, Claudia Montiel-Equihua

Comprehensive Cancer Centre

Research output: Contribution to journal › Article › peer-review

3 Citations (Scopus)

Abstract

The antitumor activity of adoptive T cell therapies (ACT) is highly dependent on the expansion, persistence, and continued activity of adoptively transferred cells. Clinical studies using ACTs have revealed that products that possess and maintain less differentiated phenotypes, including memory and precursor T cells, show increased antitumor efficacy and superior patient outcomes owing to their increased expansion, persistence, and ability to differentiate into effector progeny that elicit antitumor responses. Strategies that drive the differentiation into memory or precursor-type T cell subsets with high potential for persistence and self-renewal will enhance adoptively transferred T cell maintenance and promote durable antitumor efficacy. Because of the high costs associated with ACT manufacturing, ACTs are often only offered to patients after multiple rounds of systemic therapy. An essential factor to consider in producing autologous ACT medicinal products is the impact of the patient's initial T cell fitness and subtype composition, which will likely differ with age, disease history, and treatment with prior anti-cancer therapies. This study evaluated the impact of systemic anti-cancer therapy for non-small cell lung cancer treatment on the T cell phenotype of the patient at baseline and the quality and characteristics of the genetically modified autologous T cell therapy product after manufacturing.

Original language	English
Article number	100749
Journal	Molecular Therapy Oncolytics
Volume	31
DOIs	https://doi.org/10.1016/j.omto.2023.100749
Publication status	Published - 19 Dec 2023

Keywords

adoptive T cell therapy
cancer immunotherapy
CAR-T cells
cell therapy
immunotherapy
non-small cell lung cancer

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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O'Brien Gore, C., Billman, A., Hunjan, S., Colebrook, J., Choy, D., Li, W., Haynes, J., Wade, J., Hobern, E., McDonald, L., Papa, S., Brugman, M., Kordasti, S., & Montiel-Equihua, C. (2023). Pre-treatment with systemic agents for advanced NSCLC elicits changes in the phenotype of autologous T cell therapy products. Molecular Therapy Oncolytics, 31, Article 100749. https://doi.org/10.1016/j.omto.2023.100749

@article{5042fbc942a644ef9a20aa7fbe2e23b7,

title = "Pre-treatment with systemic agents for advanced NSCLC elicits changes in the phenotype of autologous T cell therapy products",

abstract = "The antitumor activity of adoptive T cell therapies (ACT) is highly dependent on the expansion, persistence, and continued activity of adoptively transferred cells. Clinical studies using ACTs have revealed that products that possess and maintain less differentiated phenotypes, including memory and precursor T cells, show increased antitumor efficacy and superior patient outcomes owing to their increased expansion, persistence, and ability to differentiate into effector progeny that elicit antitumor responses. Strategies that drive the differentiation into memory or precursor-type T cell subsets with high potential for persistence and self-renewal will enhance adoptively transferred T cell maintenance and promote durable antitumor efficacy. Because of the high costs associated with ACT manufacturing, ACTs are often only offered to patients after multiple rounds of systemic therapy. An essential factor to consider in producing autologous ACT medicinal products is the impact of the patient's initial T cell fitness and subtype composition, which will likely differ with age, disease history, and treatment with prior anti-cancer therapies. This study evaluated the impact of systemic anti-cancer therapy for non-small cell lung cancer treatment on the T cell phenotype of the patient at baseline and the quality and characteristics of the genetically modified autologous T cell therapy product after manufacturing.",

keywords = "adoptive T cell therapy, cancer immunotherapy, CAR-T cells, cell therapy, immunotherapy, non-small cell lung cancer",

author = "{O'Brien Gore}, Charlotte and Amy Billman and Suchete Hunjan and Jayne Colebrook and Desmond Choy and Wilson Li and Jack Haynes and Jennifer Wade and Emily Hobern and Louisa McDonald and Sophie Papa and Martijn Brugman and Shahram Kordasti and Claudia Montiel-Equihua",

note = "Funding Information: The authors would like to gratefully acknowledge the contributions of the following, without whom this publication would not have been possible: Tina Sawhney, Loiza Spanos, Andrew Walsh, Damien O{\textquoteright}Farrell, Steven Howe, Aileen Kirkpatrick, and Joseph Tarnowski. This study was funded by GSK Plc . Publisher Copyright: {\textcopyright} 2023",

year = "2023",

month = dec,

day = "19",

doi = "10.1016/j.omto.2023.100749",

language = "English",

volume = "31",

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O'Brien Gore, C, Billman, A, Hunjan, S, Colebrook, J, Choy, D, Li, W, Haynes, J, Wade, J, Hobern, E, McDonald, L, Papa, S, Brugman, M, Kordasti, S & Montiel-Equihua, C 2023, 'Pre-treatment with systemic agents for advanced NSCLC elicits changes in the phenotype of autologous T cell therapy products', Molecular Therapy Oncolytics, vol. 31, 100749. https://doi.org/10.1016/j.omto.2023.100749

TY - JOUR

T1 - Pre-treatment with systemic agents for advanced NSCLC elicits changes in the phenotype of autologous T cell therapy products

AU - O'Brien Gore, Charlotte

AU - Billman, Amy

AU - Hunjan, Suchete

AU - Colebrook, Jayne

AU - Choy, Desmond

AU - Li, Wilson

AU - Haynes, Jack

AU - Wade, Jennifer

AU - Hobern, Emily

AU - McDonald, Louisa

AU - Papa, Sophie

AU - Brugman, Martijn

AU - Kordasti, Shahram

AU - Montiel-Equihua, Claudia

N1 - Funding Information: The authors would like to gratefully acknowledge the contributions of the following, without whom this publication would not have been possible: Tina Sawhney, Loiza Spanos, Andrew Walsh, Damien O’Farrell, Steven Howe, Aileen Kirkpatrick, and Joseph Tarnowski. This study was funded by GSK Plc . Publisher Copyright: © 2023

PY - 2023/12/19

Y1 - 2023/12/19

N2 - The antitumor activity of adoptive T cell therapies (ACT) is highly dependent on the expansion, persistence, and continued activity of adoptively transferred cells. Clinical studies using ACTs have revealed that products that possess and maintain less differentiated phenotypes, including memory and precursor T cells, show increased antitumor efficacy and superior patient outcomes owing to their increased expansion, persistence, and ability to differentiate into effector progeny that elicit antitumor responses. Strategies that drive the differentiation into memory or precursor-type T cell subsets with high potential for persistence and self-renewal will enhance adoptively transferred T cell maintenance and promote durable antitumor efficacy. Because of the high costs associated with ACT manufacturing, ACTs are often only offered to patients after multiple rounds of systemic therapy. An essential factor to consider in producing autologous ACT medicinal products is the impact of the patient's initial T cell fitness and subtype composition, which will likely differ with age, disease history, and treatment with prior anti-cancer therapies. This study evaluated the impact of systemic anti-cancer therapy for non-small cell lung cancer treatment on the T cell phenotype of the patient at baseline and the quality and characteristics of the genetically modified autologous T cell therapy product after manufacturing.

AB - The antitumor activity of adoptive T cell therapies (ACT) is highly dependent on the expansion, persistence, and continued activity of adoptively transferred cells. Clinical studies using ACTs have revealed that products that possess and maintain less differentiated phenotypes, including memory and precursor T cells, show increased antitumor efficacy and superior patient outcomes owing to their increased expansion, persistence, and ability to differentiate into effector progeny that elicit antitumor responses. Strategies that drive the differentiation into memory or precursor-type T cell subsets with high potential for persistence and self-renewal will enhance adoptively transferred T cell maintenance and promote durable antitumor efficacy. Because of the high costs associated with ACT manufacturing, ACTs are often only offered to patients after multiple rounds of systemic therapy. An essential factor to consider in producing autologous ACT medicinal products is the impact of the patient's initial T cell fitness and subtype composition, which will likely differ with age, disease history, and treatment with prior anti-cancer therapies. This study evaluated the impact of systemic anti-cancer therapy for non-small cell lung cancer treatment on the T cell phenotype of the patient at baseline and the quality and characteristics of the genetically modified autologous T cell therapy product after manufacturing.

KW - adoptive T cell therapy

KW - cancer immunotherapy

KW - CAR-T cells

KW - cell therapy

KW - immunotherapy

KW - non-small cell lung cancer

UR - http://www.scopus.com/inward/record.url?scp=85178133184&partnerID=8YFLogxK

U2 - 10.1016/j.omto.2023.100749

DO - 10.1016/j.omto.2023.100749

M3 - Article

C2 - 38075248

AN - SCOPUS:85178133184

VL - 31

JO - Molecular Therapy Oncolytics

JF - Molecular Therapy Oncolytics

M1 - 100749

ER -

Pre-treatment with systemic agents for advanced NSCLC elicits changes in the phenotype of autologous T cell therapy products

Abstract

Keywords

UN SDGs

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