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Updated: Jun 13, 2025
Monitoring PD-1-Blocking Antibodies Bound to T Cells Derived from a Drop of Peripheral Blood
Published on: February 5, 2020
Peripheral Blood-Derived PD-1/CD28-CD19 CAR-Modified PD-1+ T-Cell Therapy in Patients with Solid Tumors
Zhen Zhang1, Xuan Zhao1, Qitai Zhao1
1Biotherapy Center and Cancer Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Abstract:
T cells expressing programmed cell death 1 (PD-1) in the peripheral blood (PB) of patients with tumors possess therapeutic potential; however, the immunosuppressive, PD-1-triggered signaling pathway and limited proliferative capacity of PD-1+ T cells present challenges to their therapeutic application. Here, we observed no discernible distinction between PD-1+ and PD-1- T cells in terms of clonal overlap. However, CD8+PD-1+ T cells from PB and tumor tissues exhibited tighter clustering based on clone size. Single-cell RNA sequencing analysis showed that PD-1+ T cells from PB highly expressed cytotoxicity-related genes and were enriched for T-cell activation-related pathways compared with PD-1- T cells from PB or tumor tissues. Consistent with this, PB-derived PD-1+ T cells exhibited strong cytotoxicity toward autologous tumor cells and tumor cell lines. To augment PD-1+ T-cell activity against solid tumors in vivo, we introduced a PD-1/CD28 fusion receptor combined with a CD19 chimeric antigen receptor into PD-1+ T cells, which were then expanded in vitro. The modified PD-1+ T cells exhibited superior proliferation and antitumor abilities in vitro. In addition, four patients with cancer were infused with autologous PD-1/CD28-CD19 chimeric antigen receptor PD-1+ T cells. None of these patients experienced severe side effects, and one patient with melanoma achieved a complete response that was maintained for 6.7 months. The three other patients had stable disease. Collectively, these results suggested that cell therapy with modified PB-derived PD-1+ T cells is both safe and effective, and it may constitute a promising treatment strategy for patients with cancer.
Insights
Modified peripheral blood T cells expressing programmed cell death 1 (PD-1) show enhanced anti-tumor activity and safety in cancer patients, offering a promising new cell therapy approach.
Area of Science:
- Immunology
- Oncology
- Cell Therapy
Background:
- T cells expressing programmed cell death 1 (PD-1) in peripheral blood (PB) have therapeutic potential for cancer.
- However, PD-1 signaling can suppress T cell activity and limit their proliferation, posing challenges for therapy.
Purpose of the Study:
- To investigate the characteristics of PD-1+ T cells and evaluate the efficacy of a modified PD-1+ T cell therapy in cancer patients.
Main Methods:
- Single-cell RNA sequencing was used to analyze gene expression in PD-1+ and PD-1- T cells.
- PD-1+ T cells were engineered with a PD-1/CD28 fusion receptor and CD19 chimeric antigen receptor.
- Modified T cells were expanded and infused into four cancer patients.
Main Results:
- PD-1+ T cells from PB showed higher expression of cytotoxicity genes and enrichment in T-cell activation pathways.
- Modified PD-1+ T cells demonstrated enhanced proliferation and anti-tumor activity in vitro.
- In vivo, the modified T cell therapy was safe, with one patient achieving a complete response and others stable disease.
Conclusions:
- Modified peripheral blood-derived PD-1+ T cells represent a safe and effective cell therapy for cancer.
- This approach holds promise as a novel treatment strategy for patients with solid tumors.
