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Updated: Jul 27, 2026
Multiplexed Immunofluorescence Analysis and Quantification of Intratumoral PD-1+ Tim-3+ CD8+ T Cells
Published on: February 8, 2018
Multi-parametric profiling of IL-7-augmented GD2.CART products in a phase 1 clinical trial
Sarah Schulenberg1, Martí Farrera-Sal1, Michelle Loeser1
1Berlin Institute of Health (BIH) at Charité - Universitätsmedizin Berlin, BIH Center for Regenerative Therapies (BCRT), Experimental Immunotherapy, Augustenburger Platz 1, 13353 Berlin, Germany.
Abstract:
CAR T cell (CART) therapy holds promise for cancer treatment, but heterogeneity among products limits clinical effectiveness, making systematic profiling essential to identify predictors of success. Recently, a phase 1 clinical trial investigated whether a constitutively active IL-7 receptor (C7R) could safely improve the function and persistence of GD2-directed CARTs (GD2.CARTs) in pediatric patients with high-grade CNS tumors. We analyzed infusion products from trial participants using a custom-designed 33-color full spectrum flow cytometry (FSFC) panel combined with an image-based tumor killing assay to characterize CART products and evaluate the impact of C7R on GD2.CART performance. Patient-specific variations in T cell composition were linked to therapeutic success, with C7R co-expression enhancing the functional phenotype of GD2.CARTs compared to CAR-only products. Unsupervised clustering identified CD8+ T cells associated with clinical responses, marked by activation, infiltration, resilience, and cytotoxicity. Our FSFC-based profiling approach reveals determinants of CART efficacy and supports strategies to optimize adoptive immunotherapy.
Insights
Constitutively active IL-7 receptor (C7R) enhanced Chimeric Antigen Receptor T cell (CART) therapy for pediatric brain tumors. Profiling identified CD8+ T cells associated with better treatment outcomes.
Area of Science:
- Immunology
- Oncology
- Biotechnology
Background:
- Chimeric Antigen Receptor T cell (CART) therapy shows promise for cancer treatment.
- Product heterogeneity in CART therapy limits clinical effectiveness, necessitating systematic profiling to find success predictors.
Purpose of the Study:
- To investigate if a constitutively active IL-7 receptor (C7R) can safely improve the function and persistence of GD2-directed CARTs (GD2.CARTs) in pediatric high-grade CNS tumors.
- To characterize CART products and assess C7R's impact on GD2.CART performance using advanced flow cytometry and killing assays.
Main Methods:
- Analysis of infusion products from a phase 1 clinical trial using a 33-color full spectrum flow cytometry (FSFC) panel.
- Evaluation of CART product function via an image-based tumor killing assay.
- Unsupervised clustering to identify T cell subsets associated with clinical responses.
Main Results:
- Patient-specific T cell composition correlated with therapeutic success.
- C7R co-expression improved the functional phenotype of GD2.CARTs compared to CAR-only products.
- CD8+ T cells exhibiting activation, infiltration, resilience, and cytotoxicity were linked to clinical responses.
Conclusions:
- FSFC-based profiling reveals key determinants of CART efficacy.
- C7R co-expression represents a viable strategy to enhance CART function and persistence.
- This approach supports the optimization of adoptive immunotherapy for challenging cancers.
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