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Single-Cell Transcriptomics Reveals Immune Reconstitution in Patients with R/R T-ALL/LBL Treated with Donor-Derived
Wei Chen1, Hui Shi2, Zhuojun Liu1
1Beijing Advanced Innovation Centre for Biomedical Engineering, Key Laboratory for Biomechanics and Mechanobiology of Ministry of Education, School of Engineering Medicine, Beihang University, Beijing, China.
Summary
CD7 CAR-T therapy shows promise for T-cell leukemia/lymphoma, leading to T cell depletion and expansion of functional CD7- T cells. This study details immune reconstitution dynamics crucial for optimizing treatment.
Area of Science:
- Immunology
- Oncology
- Cellular Biology
Background:
- CD7 chimeric antigen receptor T (CAR-T) therapy demonstrates significant antitumor effects in relapsed/refractory (R/R) T-cell acute lymphoblastic leukemia/lymphoma (T-ALL/LBL).
- The dynamics of immune reconstitution following CAR-T therapy remain incompletely understood, posing a challenge for treatment optimization.
Purpose of the Study:
- To evaluate the safety and efficacy of donor-derived CD7 CAR-T cells in patients with R/R T-ALL/LBL.
- To investigate the immune reconstitution profile after CD7 CAR-T therapy using advanced techniques like single-cell RNA sequencing.
Main Methods:
- An open-label Phase I clinical trial involving 7 R/R T-ALL/LBL patients.
- Monitoring of CAR-T cell presence via flow cytometry and PCR.
- Quantification of cytokine levels using cytometric bead arrays.
- Profiling immune reconstitution through single-cell RNA sequencing (scRNA-seq).
Main Results:
- 100% complete remission observed by day 28; median follow-up was 4 months.
- Common toxicities included leukopenia, thrombocytopenia, and neutropenia; 5 patients experienced infections, with 3 deaths attributed to serious infection or hemorrhage.
- Efficient CAR-T cell expansion occurred in all patients, leading to CD7+ T cell elimination and significant expansion of CD7- T cells.
- scRNA-seq revealed enhanced immunologic activity in CD7- T cells, characterized by activated autoimmune pathways.
- Monocyte loss was associated with fatal infections, and S100A8/S100A9 were identified as potential relapse markers.
Conclusions:
- CD7 CAR-T therapy is effective in R/R T-ALL/LBL, inducing profound immune changes.
- Understanding the cellular dynamics of immune homeostasis post-therapy is key to refining treatment strategies.
- Identification of monocyte loss and S100A8/S100A9 as relapse markers offers potential avenues for monitoring and management.
