Therapeutic Efficacy of CD34-Derived Allogeneic Dendritic Cells Engineered to Express CD93, CD40L, and CXCL13 in Humanized Mouse Models of Pancreatic Cancer
<b>Background/Objectives</b>: Pancreatic cancer remains the fourth leading cause of cancer-related deaths. While peripheral blood-derived mature dendritic cell (mDC) vaccines have shown potential in eliciting anti-tumor immune responses, clinical efficacy has been limited. This study aim...
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| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2025-07-01
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| Series: | Vaccines |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2076-393X/13/7/749 |
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| Summary: | <b>Background/Objectives</b>: Pancreatic cancer remains the fourth leading cause of cancer-related deaths. While peripheral blood-derived mature dendritic cell (mDC) vaccines have shown potential in eliciting anti-tumor immune responses, clinical efficacy has been limited. This study aimed to enhance the potency and scalability of DC-based immunotherapy by developing an allogeneic DC platform derived from CD34<sup>+</sup> hematopoietic stem cells (HSCs), genetically engineered to overexpress CD93, CD40L, and CXCL13, followed by maturation and tumor antigen pulsing. <b>Methods</b>: Engineered DCs were generated from CD34<sup>+</sup> HSCs and matured in vitro after lentiviral transduction of CD93, CD40L, and CXCL13. Tumor lysates were used for antigen pulsing. A scrambled-sequence control DC was used for comparison. In vitro assays were performed to assess T cell activation and tumor cell killing. In vivo efficacy was evaluated using orthotopic pancreatic tumors in BLT and PBMC-humanized NSG mice established with the MiaPaca-2 (MP2) cell line. <b>Results</b>: Engineered DCs significantly enhanced T cell activation and tumor-specific cytotoxicity in vitro compared to control DCs. Antigen pulsing further amplified immune activation. In vivo, treated humanized mice showed increased CD4<sup>+</sup>, CD8<sup>+</sup>, and NK cell frequencies in peripheral blood and within tumors, correlating with reduced tumor burden. <b>Conclusions</b>: Our data shows that the antigen-pulsed, engineered DCs have the potency to activate immune cells, which leads to a significant reduction in pancreatic tumors and therefore could potentially provide an effective therapeutic opportunity for the treatment of pancreatic cancer and other solid tumors. |
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| ISSN: | 2076-393X |