Aim: To immunize the mice with gp96-peptide complexes extracted and purified from different kinds of malignant tumor cells and to observe anti-tumor immunity induced by the complexes.
Methods: HSP gp96-peptide complexes were extracted and purified from different kinds of malignant tumor cells. Mice were immunized subcutaneously with the complexes from different sources at different doses. Then the mice were challenged with 2 x 10(5) tumor cells on the seventh day after the last immunization. Tumor incidence, weight and histology were observed and compared with those of control group. At the meantime, cytotoxicity activity and nitric oxide production of mouse peritoneal macrophages were detected in vitro after being stimulated with gp96-peptide complexes.
Results: The SDS-PAGE and Western blot showed that gp96-peptide complexes were purified successfully. The anti-tumor immunity was correlated with the dose of the complex and the immunized mice could resist the challenge of homogeneous tumor cells. NO secreted from the peritoneal macrophages stimulated with the complex was significantly higher than that of control group and the tumoricidal activity of the macrophages in vitro was markedly promoted by the complex.
Conclusion: Mice immunized with appropriate dose of gp96-peptide complexes from H22 tumor cells can resist the challenge of syngeneic tumor cells. NO secreted by macrophages stimulated with the complex might play a key role in the anti-tumor immunity.
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Biomaterials
January 2025
Department of Pharmacy of Puning People's Hospital (Guangdong Postdoctoral Innovation Practice Base of Jinan University), Department of Chemistry, State Key Laboratory of Bioactive Molecules and Druggability Assessment, MOE Key Laboratory of Tumor Molecular Biology, Jinan University, Guangdong, 510632, China. Electronic address:
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Department of Oncology, Cross Cancer Institute, University of Alberta, Edmonton, AB T6G 1Z2, Canada; Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, AB T6G 2R3, Canada. Electronic address:
Patients with colorectal cancers (CRCs) that have microsatellite instability (MSI) (MSI CRCs) face a better prognosis than those with the more common chromosomal instability (CIN) subtype (CIN CRCs) due to improved T cell-mediated anti-tumor immune responses. Previous investigations identified the cytosolic DNA (cyDNA) sensor STING as necessary for chemokine-mediated T cell recruitment in MSI CRCs. Here, we find that cyDNA from MSI CRC cells is inherently more capable of inducing STING activation and improves cytotoxic T cell activation by dendritic cells (DCs).
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Department of Pharmacology, Physiology, and Cancer Biology, Thomas Jefferson University, Philadelphia, PA, USA.
Adaptive immune resistance in cancer describes the various mechanisms by which tumors adapt to evade anti-tumor immune responses. IFN-γ induction of programmed death-ligand 1 (PD-L1) was the first defined and validated adaptive immune resistance mechanism. The endoplasmic reticulum (ER) is central to adaptive immune resistance as immune modulatory secreted and integral membrane proteins are dependent on ER.
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Brown Center for Immunotherapy. Indiana University School of Medicine. 975 W. Walnut St., IB554A, Indianapolis, IN 46202. Electronic address:
Chimeric Antigen Receptor (CAR) T cell therapy has revolutionized cancer treatment and is now being explored for other diseases, such as autoimmune disorders. While the tumor microenvironment (TME) in cancer is often immunosuppressive, in autoimmune diseases, the environment is typically inflammatory. Both environments can negatively impact CAR T cell survival: the former through direct suppression, hypoxia, and nutrient deprivation, and the latter through chronic T cell receptor (TCR) engagement, risking exhaustion.
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Shanghai Frontiers Science Center of Genome Editing and Cell Therapy, Shanghai Key Laboratory of Regulatory Biology and School of Life Sciences, East China Normal University, Shanghai, China, 200241. Electronic address:
CAR T-cell therapy has achieved remarkable clinical success in treating hematological malignancies. However, its clinical efficacy in solid tumors is less satisfactory, partially due to poor in vivo expansion and limited persistence of CAR-T cells. Here, we demonstrated that the overexpression of glucocorticoid-induced tumor necrosis factor receptor-related protein ligand (GITRL) enhances the anti-tumor activity of CAR-T cells.
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