<p>Virus-Like Particles Presenting the FGF-2 Protein or Identified Antigenic Peptides Promoted Antitumor Immune Responses in Mice</p>

Abstract

Background: Fibroblast growth factor (FGF)-2 is overexpressed in various tumor tissues. It affects tumor cell proliferation, invasion and survival, promotes tumor angiogenesis and is tightly involved in the development of systemic and local immunosuppressive tumor mechanisms. Purpose: This study aimed to develop an effective vaccine against FGF-2 and to investigate the effects of anti-FGF-2 immunization on tumor growth and antitumor immune responses. Methods: A set of thirteen synthesized overlapping peptides covering all possible linear B-cell epitopes of murine FGF-2 and a recombinant FGF-2 protein were conjugated to viruslike particles (VLPs) of recombinant hepatitis B core antigen (HBcAg). The VLPs were immunized through a preventive or therapeutic strategy in a TC-1 or 4T1 grafted tumor model. Results: Immunization with FGF-2 peptides or full-length protein-coupled VLPs produced FGF-2-specific antibodies with a high titer. Peptide 12, which is located in the heparin-binding site of FGF-2, or protein-conjugated VLPs presented the most significant effects on the suppression of TC-1 tumor growth. The levels of IFN-γ-expressing splenocytes and serum IFN-γ were significantly elevated; further, the immune effector cells CD8 + IFN-γ + cytotoxic T lymphocytes (CTLs) and CD4 + IFN-γ + Th1 cells were significantly increased, whereas the immunosuppressive cells CD4 + CD25 + FOXP3 + Treg cells and Gr-1 + CD11b + myeloidderived suppressor cells (MDSCs) were decreased in the immunized mice. In addition, VLP immunization significantly suppressed tumor vascularization and promoted tumor cell apoptosis. In mice bearing 4T1 breast tumor, preventive immunization with FGF-2-conjugated VLPs suppressed tumor growth and lung metastasis, and increased effector cell responses. Conclusion: Active immunization against FGF-2 is a new possible strategy for tumor immunotherapy.

P. aeruginosa Mediated Necroptosis in Mouse Tumor Cells Induces Long-Lasting Systemic Antitumor Immunity

“…Then, we found that bacteria also triggered high levels of caspase-3-dependent apoptosis and other cell death like necroptosis and NETosis in tumor tissues; in the meantime, cell proliferation was also decreased according to Ki67 detection (Figure 4). Our previous works indicated that no (39)(40)(41)(42)(43)(44). At last, our results also indicated oncolytic bacteria P. aeruginosa produced durable tumor regression and reshaped the systemic and tumorinfiltrating immune cells profile changes, especially IFN-g-and IL-2-producing lymphocytes (Figure 5).…”

Starfysh reveals heterogeneous spatial dynamics in the breast tumor microenvironment

“…26, 27; see Methods ), revealing immunosuppressive pathways such as FGF2, TIMP1, FGFR1, CD44 . Notably, FGF2 is a pro-tumor angiogenesis factor and induces drug resistance in chemotherapy in breast cancer 57 . TIMP1 is also found to be correlated with cancer progression and significantly increased in tumor-infiltrating lymphocytes (TILs) and Tregs 58 59 .…”

Recombinant VLPs empower RBM peptides showing no immunogenicity in native SARS-COV-2 protein to elicit a robust neutralizing antibody response

“…). In addition, recombinant virus-like particles (VLPs) are also an ideal vaccine delivery system ( 32 , 40 , 41 ). However, the linear B cell epitopes generally induce the antibodies showing weaker binding affinity and correspondingly weaker neutralizing activity as compared to conformational epitopes, which limits the use of linear epitopes as a vaccine antigen ( 42 ).…”