Wei-Qiang Gao, Bin Ma’s team from the school of Biomedical Engineering, Shanghai Jiaotong University published their research findings "Targeted delivery of CXCL9 and OX40L by metabolic stem cells extracts potent antibody or immunity" in a well-known international journal Molecular Therapy of American Association for Gene and Cell Therapy (ASGCT). The paper’s first author is doctoral student Pan Yin, Professor Wei-Qiang Gao, and associate researcher Bin Ma are co corresponding authors.

Chimeric antigen receptor (CAR)-modified T cells and immune regulatory checkpoint blockade are at the forefront of immunotherapy for cancers of various histological types. Antibodies targeting T cell inhibitory receptors programmed death-1 (PD-1) or cytotoxic T lymphocyte-associated protein 4 (CTLA-4) can result in impressive tumor control in patients. However, in most cases the therapeutic efficacy is limited by many obstacles such as low infiltration of immune effector cells in solid tumors.

Mesenchymal stem cells (MSCs) are emerging as promising cellular vehicles that possess an intrinsic preferential migratory ability toward a number of different tumor types upon systemic administration. Their availability from many different adult tissues, ease of expansion in culture, the ability to avoid immune rejection, and their tumortropic migratory properties and long lifespan at the site of residence make MSCs a great resource for cell-based therapy.

This paper reported a mesenchymal stem cell (MSC)-based immunotherapeutic strategy in which MSCs specifically deliver T/natural killer (NK) cell-targeting chemokine CXCL9 and immunostimulatory factor OX40 ligand (OX40L)/ tumor necrosis factor superfamily member 4 (TNFSF4) to tumor sites in syngeneic subcutaneous and azoxymethane (AOM)/dextran sulfate sodium (DSS)-induced spontaneous colon cancer mouse models. This approach generated potent local antitumor immunity by increasing the ratios of tumor infiltrating CD8 + T and NK cells and production of antitumor cytokines and cytolytic proteins in the tumor microenvironment. Moreover, it improved the efficacy of programmed death-1 (PD-1) blockade in a syngeneic mouse model and significantly suppressed the growth of major histocompatibility complex class I (MHC class I)-deficient tumors. MSC-based immunotherapeutic strategy simultaneously recruited and activated immune effector cells at the tumor site, thus overcoming the problems with toxicities of systemic therapeutic agents and low lymphocyte infiltration of solid tumors.

Full text link:

https://www.cell.com/molecular-therapy-family/molecular-therapy/fulltext/S1525-0016(20)30415-9