Analysis of the composition of intratumoral lymphoid cells isolated from tumors after SFV/IFNg treatment revealed increased CD4+ and CD8+ and decreased T-reg (CD4+/CD25+/FoxP3+) cell populations. In the orthotopic 4T1 mouse model, intratumoral administration of SFV/IFNg virus particles alone or in combination with the Pam3CSK4 TLR2/1 ligand led to significant inhibition of tumor growth compared to the administration of the control SFV/Luc virus particles. Coculturing SFV/IFNg-infected 4T1 spheroids with BMDMs inhibited spheroid growth. We demonstrated that SFV-derived, IFN-g-stimulated bone marrow macrophages can be used to acquire the tumoricidal M1 phenotype in 3D nonattached conditions. We developed a replication-deficient Semliki Forest virus vector expressing IFNg (SFV/IFNg) and evaluated its immunomodulatory antitumor potential in vitro in a model of 3D spheroids and in vivo in an immunocompetent 4T1 mouse breast cancer model. Interferon gamma (IFNg) is a pleiotropic cytokine that can potentially reprogram the tumor microenvironment however, the antitumor immunomodulatory properties of IFNg still need to be validated due to variable therapeutic outcomes in preclinical and clinical studies. We highlight the advantages and limitations of virus vectors for targeted therapeutic programming of tumour immune cell populations and tumour stroma, and propose future steps to establish viral vectors as a standard, efficient, safe, and non-toxic cancer immunotherapy approach that can complement other promising treatment strategies, e.g., checkpoint inhibitors, CAR-T, and advanced chemotherapeutics. In this review, we consider DNA and RNA virus vectors delivering immunomodulatory genes (cytokines, chemokines, co-stimulatory molecules, antibodies, etc.) and discuss how these viruses break an immunosuppressive cell development and switch TME to an immune-responsive “hot” state. Tumour-associated immune cells, as the main component of TME, support tumour progression through multiple pathways inducing resistance to treatment and promoting cancer cell escape mechanisms. One of the key elements of successful virus-based cancer immunotherapy is the understanding of the tumour immune state and the development of vectors to modify the immunosuppressive tumour microenvironment (TME). A number of challenges have to be solved to translate promising vectors to clinics. Although many preclinical studies demonstrate significant virus-mediated tumour inhibition in synergy with immune checkpoint molecules and other drugs, the clinical success of viral vector applications in cancer therapy currently is limited. The results confirm that the developed techniques are promising for determining thermodynamic characteristics of one of the binary systems without experimental study.Viral vectors have been widely investigated as tools for cancer immunotherapy. ![]() Dependences of the integral excess Gibbs energy and entropy, integral molar Gibbs energy, mixing entropy and mixing enthalpy on the antimony mole fraction are calculated at 973 K for the Bi-Sb system, which cannot be studied by the EMF method due to the proximity of Bi and Sb potentials in the electrochemical series. A simplified procedure for calculating integral molar thermodynamic functions of binary and ternary systems by the Darken method using only standard Excel tools is described in detail. Proposed extensions allowed studying alloys of three different compositions simultaneously and increasing the reliability of the experimental EMF values. An improved construction of the electrochemical cell and optimized technique for measuring the electromotive forces (EMF) of liquid metallic Pb-Bi-Sb, Pb-Bi and Pb-Sb alloys in the KCl-PbCl 2 melt are described in this paper.
0 Comments
Leave a Reply. |
Details
AuthorWrite something about yourself. No need to be fancy, just an overview. ArchivesCategories |