The vesicles named "IL2-ep13nsEV" induced a strong immune reaction in vivo to rescue approximately 50% of mice implanted with patient-derived xenografts while sensitizing cancer cells to immune checkpoint inhibitor treatment to prevent tumor recurrence. Upon administration, they saw how the surface-bound IL2 guided nanovesicles toward lymphoid organs associated with immune cells to activate similar immune receptors on lymphocytes. The nanovesicles displayed major-hiscompatibility complex-bound antigens from dendritic immune cells. The research team accomplished this by anchoring membrane-bound bioactive protein interleukin-2 (IL2 made by a type of T lymphocyte) to maintain enriching and T-cell promoting co-stimulatory factors on dendritic cell-derived small extracellular vesicle surfaces. In a new report in Science Advances, Kerui Wu and colleagues in the departments of cancer biology, translation biology and breast surgery in the U.S., and China engineered active immunotherapy to create smart nanovesicles for personalized treatment. DOI: 10.1126/sciadv.ade0625īreast cancer is resistant to immunotherapies therefore, bioengineers and oncologists seek to develop a slew of therapeutic strategies to overcome this challenge. It can be used to prevent the recurrence of surgically removed primary tumor or to treat advanced breast cancer resistant to ICI. IL2-ep13nsEV is designed to act as active immunotherapy to expand the pool of cancer-specific immune cells by facilitating neoantigen processing and presentation, as well as T cell activation. Therefore, this sEV, geared with tumor lysate–derived antigens and bioactive membrane–bound IL2 and enhanced with costimulatory factors, is named as IL2-ep13nsEV.
We found that LPS and STING agonist worked together to promote the expression of costimulatory factors on the surface of this engineered vesicle.
This personalization of DC-derived sEV (p13nsEV) is achieved by loading lysed surgically harvested breast cancer cells onto engineered autologous DCs followed by collecting sEVs that are then used as personalized immunotherapy. To generate this active immunotherapy, the sEVs from autologous DCs are engineered with surface membrane–bound IL2 by expressing IL2-MFG-E8. Design of IL2-ep13nsEV and its utilization in treating breast cancer.
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