nl8b02321_si_001.pdf (2.22 MB)
Engineering PD-1-Presenting Platelets for Cancer Immunotherapy
journal contribution
posted on 2018-07-31, 15:22 authored by Xudong Zhang, Jinqiang Wang, Zhaowei Chen, Quanyin Hu, Chao Wang, Junjie Yan, Gianpietro Dotti, Peng Huang, Zhen GuRadical
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.