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\begin{document}

\title{Bioengineer mesenchymal stem cell for Treatment of glioma by IL-12
mediated microenvironment reprogramming and nCD47-SLAMF7 mediated
phagocytosis regulation of macrophages}



\author[1]{Man Li}%
\author[2]{Lisen Lu}%
\author[1]{Qungen Xiao}%
\author[1]{ALI ABDI MAALIM}%
\author[1]{Bin Nie}%
\author[1]{Yanchao Liu}%
\author[1]{Kai  Shu}%
\author[1]{Ting  Lei}%
\author[1]{Mingxin Zhu}%
\affil[1]{Huazhong University of Science and Technology}%
\affil[2]{Huazhong Agricultural University}%


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  \date{June 16, 2024}


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\begin{abstract}
High expression of cellular self-activated immunosuppressive molecules
and extensive infiltration of suppressive immune cells in the tumor
microenvironment are the main factors leading to the resistance of
glioma to immunotherapy. However, the technology related to modifying
the expression of glioma cellular self-molecules based on gene editing
still needs to be developed. In this project, cell therapy strategies
were developed to reverse the immunosuppressive microenvironment of
glioma (TIME). Mesenchymal stem cells (MSCs) derived from bone marrow
were used as carriers to express bioactive proteins, which could exhibit
tumor-homing characteristics in response to tumor TGF-\selectlanguage{greek}β \selectlanguage{english}signals. MSCs
were modified to express the secretory anti-tumor immune cytokine IL-12
and the nCD47-SLAMF7 fusion protein, which regulates the phagocytosis of
macrophages. The engineered MSCs are then injected in situ into the area
near the glioma to bypass the blood-brain barrier and provide localized
high concentrations of bioactive proteins. This approach could
significantly activate natural and adaptive immune cells in the TIME,
ultimately leading to the effective control of glioma. This study
provides a new strategy for the clinical treatment of glioma patients
and the prevention of postoperative recurrence.%
\end{abstract}%



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