Murine Leukemia-Derived Extracellular Vesicles Elicit Antitumor Immune Response

Abstract

Background: Extracellular vesicles (EVs) are heterogeneous lipid bilayer particles secreted by cells. EVs contain proteins, RNA, DNA and other cargo that can have immunomodulatory effects. Cancer-derived EVs have been described as having immunomodulating effects in vivo with immunosuppressive and pro-tumor growth capabilities. However, cancerderived EVs have also been harnessed and utilized for anti-cancer potential. Methods: To assess the immunomodulatory effect of EVs produced by acute myeloid leukemia (AML) cells, we isolated vesicles secreted by the murine AML cell line, C1498, and investigated their effect on in vitro and in vivo immune responses. Results: These leukemia-derived EVs were found to induce increased proliferation of CD3+ cells and enhanced cytolytic activity of CD3+ cells directed toward leukemic cells in vitro. Injection of leukemia-derived EVs into syngeneic naïve mice induced T cell responses in vivo and resulted in enhanced immune responses upon T cell re-stimulation in vitro. Conclusion:These findings indicate that C1498-derived EVs have immunomodulatory effects on cell-mediated immune responses that could potentially be utilized to facilitate antileukemia immune responses.

Drug delivery methods for cancer immunotherapy

“…Reduced tumor growth and extended survival [ 33 ] Exosomes (TEXs) - Modification of gene expression of CD8 + , CD4 + and CD4 + CD39 + T cells. Significant CD8 + immune responses [ 34 , 35 ] CHOL/L-α-phosphatidylcholine (PC)-based liposomal formulation Lymphoma OVA/adjuvants (poly(I:C) and CpG ODN) (cancer vaccine) Synergistic effect of the adjuvants with the carrier. Immunization for 8 months with deceleration in tumor progression [ 20 ] C3-targeted liposomes (DPPC/1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC)/DSPE-PEG2000) OVA antigen (cancer vaccine) Antigens delivered and internalized in APCs.…”

“…In this regard, Pando et al have recently reported the modification of gene expression of CD8 + , CD4 + , and CD4 + CD39 + T cells by using AML-derived extracellular vesicles. The authors reported in vitro and in vivo the impact of these TEXs on the induction of significant CD8 + immune responses [ 34 , 35 ].…”