Engineering PD-1-Presenting Platelets for Cancer Immunotherapy
Year: 2018
Type: article
Abstract: Radical surgery still represents the treatment choice for several malignancies. However, local and distant tumor relapses remain the major causes of treatment failure, indicating that a postsurgery consolidation treatment is necessary. Immunotherapy with checkpoint inhibitors has elicited impressive clinical responses in several types of human malignancies and may represent the ideal consolidation treatment after surgery. Here, we genetically engineered platelets from megakaryocyte (MK) progenitor cells to express the programmed cell death protein 1 (PD-1). The PD-1 platelet and its derived microparticle could accumulate within the tumor surgical wound and revert exhausted CD8 + T cells, leading to the eradication of residual tumor cells. Furthermore, when a low dose of cyclophosphamide (CP) was loaded into PD-1-expressing platelets to deplete regulatory T cells (Tregs), an increased frequency of reinvigorated CD8 + lymphocyte cells was observed within the postsurgery tumor microenvironment, directly preventing tumor relapse.
Source: Nano Letters
Institutions: University of North Carolina at Chapel Hill, North Carolina State University, California NanoSystems Institute, University of California, Los Angeles, Shenzhen University, Lampe Joint Department of Biomedical Engineering, Shenzhen University Health Science Center, UNC Lineberger Comprehensive Cancer Center
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W2885447533