Nearly a century has passed since the first report describing antigen-specific immunotherapy (antigen-SIT) was published. Research into the use of antigen-SIT in the treatment of both allergic and autoimmune disease has increased dramatically since, although its mechanism of action is only slowly being unravelled. It is clear though, from recent studies, that success of antigen-SIT depends on the induction of regulatory T (T reg) cell subsets that recognise potentially disease-inducing epitopes. The major challenge remaining for the widespread use of antigen-SIT is to safely administer high doses of immunodominant and potentially pathogenic epitopes in a manner that induces T cell tolerance rather than activation. This review illustrates that intelligent design of treatment agents and strategies can lead to the development of safe and effective antigen-SIT.
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http://dx.doi.org/10.1016/j.coi.2010.08.006 | DOI Listing |
Mol Cancer
January 2025
Department of Medicine, Section of Epidemiology and Population Sciences, Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX, 77030, USA.
Lipid nanoparticles (LNPs) for mRNA delivery have advanced significantly, but LNP-mediated DNA delivery still faces clinical challenges. This study compared various LNP formulations for delivering DNA-encoded biologics, assessing their expression efficacy and the protective immunity generated by LNP-encapsulated DNA in different models. The LNP formulation used in Moderna's Spikevax mRNA vaccine (LNP-M) demonstrated a stable nanoparticle structure, high expression efficiency, and low toxicity.
View Article and Find Full Text PDFJ Transl Med
January 2025
Department of Medical Oncology, Division of Life Sciences and Medicine, The First Affiliated Hospital of USTC, University of Science and Technology of China, Anhui Provincial Cancer Hospital, Hefei, 230031, Anhui, China.
Background: Agonistic monoclonal antibodies targeting 4-1BB/CD137 have shown preclinical promise, but their clinical development has been limited by severe liver toxicity or limited efficacy. Therefore, a safe and efficient immunostimulatory molecule is urgently needed for cancer immunotherapy.
Methods: A novel anti-MSLN×4-1BB bispecific antibody (bsAb) was generated via antibody engineering, and its affinity and activity were detected via enzyme-linked immunosorbent assay (ELISA), flow cytometry, and T-cell activation and luciferase reporter assays.
Sci Rep
January 2025
The Jenner Institute, University of Oxford, Oxford, UK.
BCG remains the only licensed vaccine for tuberculosis (TB), but its efficacy wanes over time. Subunit vaccines, aim to improve BCG immunity and protection, by inducing responses to a few mycobacterial antigens delivered with a specific platform. Since the platform shapes the immune response induced, selecting the right platform has been challenging due to the lack of immune correlates of protection.
View Article and Find Full Text PDFJ Control Release
January 2025
College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 08826, Republic of Korea. Electronic address:
Post-surgical tumor recurrence poses a major challenge in cancer treatment due to residual tumor cells and surgery-induced immunosuppression. Here, we developed hybrid nanoparticles, termed T-DCNPs, designed to promote antigen-specific activation of cytotoxic CD8+ T cells while concurrently inhibiting immunosuppressive pathways within the tumor microenvironment. T-DCNPs were formulated by co-extruding lipid nanoparticles containing a transforming growth factor β inhibitor with dendritic cells that were pre-treated with autologous neoantigens derived from surgically excised tumors.
View Article and Find Full Text PDFInt Immunopharmacol
January 2025
Department of Liver Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences &Peking Union Medical College, Beijing, China. Electronic address:
A shift toward a T cell exhaustion phenotype is associated with the upregulation of expression of programmed cell death protein 1 (PD-1) on T lymphocytes in patients with malignant solid tumors. The interaction between PD-1 and programmed death-ligand 1 (PD-L1) inhibits PD-1 T lymphocyte function, impacting their anti-tumor immune activity. Immune checkpoint inhibitors targeting PD-1/PD-L1 have revolutionized the treatment of various solid malignancies, improving therapeutic efficacy and survival outcomes.
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