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

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...

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Bibliographic Details
Published in:	Molecular therapy. Oncolytics Vol. 31; p. 100749
Main Authors:	O’Brien Gore, Charlotte, Billman, Amy, Hunjan, Suchete, Colebrook, Jayne, Choy, Desmond, Li, Wilson, Haynes, Jack, Wade, Jennifer, Hobern, Emily, McDonald, Louisa, Papa, Sophie, Brugman, Martijn, Kordasti, Shahram, Montiel-Equihua, Claudia
Format:	Journal Article
Language:	English
Published:	United States Elsevier Inc 19-12-2023 Elsevier
Subjects:	adoptive T cell therapy cancer immunotherapy CAR-T cells cell therapy immunotherapy non-small cell lung cancer non-small cell lung cancer adoptive T cell therapy CAR-T cells cell therapy immunotherapy cancer immunotherapy
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Summary:	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. [Display omitted] Montiel-Equihua and colleagues: T cell medicines are personalized anti-cancer therapies made from the patient’s cells. Small-scale medicines produced from patients who received common anti-cancer drugs show differences in cell composition and, in most cases, no changes in cytotoxicity in vitro. The effect of the changes on efficacy or persistence in vivo is unknown.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	2372-7705 2372-7705
DOI:	10.1016/j.omto.2023.100749