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

Research output: Contribution to journalArticlepeer-review

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 languageEnglish
Article number100749
JournalMolecular Therapy Oncolytics
Volume31
DOIs
Publication statusPublished - 19 Dec 2023

Keywords

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

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