A Biomimetic Autophagosomes‐Based Nanovaccine Boosts Anticancer Immunity

Advanced Materials, Год журнала: 2024, Номер unknown

Опубликована: Авг. 28, 2024

Personalized cancer vaccines based on tumor cell lysates offer promise for immunotherapy yet fail to elicit a robust therapeutic effect due the weak immunogenicity of antigens. Autophagosomes, obtained from pleural effusions and ascites patients, have been identified as abundant reservoirs neoantigens that exhibit heightened immunogenicity. However, their potential personalized constrained by suboptimal lymphatic-targeting performances challenges in antigen-presenting endocytosis. Here,a reinforced biomimetic autophagosome-based (BAPs) nanovaccine generated precisely amalgamating autophagosome-derived two types adjuvants capable targeting lymph nodes is developed potently antitumor immunity. The redox-responsive BAPs facilitate cytosolic vaccine opening within cells, thereby exposing antigens stimulate strong immune response. evoke broad-spectrum T-cell responses, culminating effective eradication 71.4% established tumors. Notably, vaccination triggers enduring responses confer protection, with 100% mice shielded against rechallenge significant reduction incidence 87.5%. Furthermore, synergize checkpoint blockade therapy inhibit growth poorly immunogenic breast model. approach presents powerful formula high versatility immunotherapy.

Язык: Английский

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Unlocking the secrets of the immunopeptidome: MHC molecules, ncRNA peptides, and vesicles in immune response

Frontiers in Immunology, Год журнала: 2025, Номер 16

Опубликована: Янв. 29, 2025

The immunopeptidome, a diverse set of peptides presented by Major Histocompatibility Complex (MHC) molecules, is critical component immune recognition and response. This review article delves into the mechanisms peptide presentation MHC particularly emphasizing roles ncRNA-derived extracellular vesicles (EVs) in shaping immunopeptidome landscape. We explore established emerging insights molecule interactions with peptides, including dynamics loading, transport, influence cellular genetic variations. highlights novel research on non-coding RNA (ncRNA)-derived which challenge conventional views antigen processing role EVs transporting these thereby modulating responses at remote body sites. not only challenges but also opens up new avenues for understanding responses. Furthermore, we discuss implications developing therapeutic strategies, cancer immunotherapy. By conducting comprehensive analysis current literature advanced methodologies immunopeptidomics, this aims to deepen complex interplay between system, offering perspectives potential diagnostic applications. Additionally, provide mechanism enhanced surface highlight pathway their systemic distribution, potentially altering surveillance landscapes.

Язык: Английский

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Optimizing rWTC-MBTA Vaccine Formulations, Dosing Regimens, and Cryopreservation Techniques to Enhance Anti-Metastatic Immunotherapy

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(3), С. 1340 - 1340

Опубликована: Фев. 5, 2025

Metastatic cancer poses significant clinical challenges, necessitating effective immunotherapies with minimal systemic toxicity. Building on prior research demonstrating the rWTC-MBTA vaccine’s ability to inhibit tumor metastasis and growth, this study focuses its translation by optimizing vaccine composition, dosing regimens, freezing techniques. The formula components included three TLR ligands (LTA, Poly I:C, Resiquimod) an anti-CD40 antibody, which were tested in melanoma triple-negative breast (TNBC) models. formulations categorized as rWTC-MBT (Mannan-BAM LTA, Resiquimod), rWTC-MBL (LTA), rWTC-MBP I:C), rWTC-MBR (Resiquimod). In models, all exhibited efficacy that was comparable of full vaccine, while “colder” TNBC multiple or Resiquimod alone performed best. Vaccine-induced activation dendritic cell (DC) subsets, including conventional DCs (cDCs), myeloid (mDCs), plasmacytoid (pDCs), accompanied CD80+CD86+ population induction, suggesting robust innate immune stimulation. An initial three-dose schedule followed booster doses (3-1-1-1 3-3-3-3) reduced metastatic burden effectively. Gradual (DMSO-based preservation) maintained efficacy, underscoring importance intact structure. These findings highlight potential simplified formulations, optimized dosing, techniques developing practical, scalable for cancers.

Язык: Английский

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Autologous Nanovaccine Induces Immunogenic Domino Effect to Prevent Postoperative Recurrence of Orthotopic Glioblastoma

Advanced Functional Materials, Год журнала: 2025, Номер unknown

Опубликована: Фев. 3, 2025

Abstract Glioblastoma (GBM), the most aggressive form of primary intracranial tumors, poses significant challenges for effective treatment. The highly invasive characteristics GBM render complete tumor resection exceedingly difficult and frequently lead to postoperative recurrence. To address this issue, a novel autologous nano vaccine is developed convert immunosuppressive microenvironment into an active immune landscape through immunogenic domino effect, thereby targeting residual cells preventing This nanovaccine formulated by co‐loading lipopolysaccharide (LPS) glioblastoma cell lysates (GCL) layered double hydroxide (LDH) nanosheets, which are subsequently integrated within injectable alginate hydrogel create LLGA‐Gel. exploits potential GCL in conjunction with immunostimulatory properties LPS induce pyroptotic death, enhance dendritic maturation, promote macrophage polarization toward M1 phenotype; these effects culminate increased CD8 + T infiltration reduced Foxp3 Tregs at site. In vivo experiments demonstrate that not only enhances efficacy death but also significantly amplifies response, markedly reducing recurrence orthotopic GBM. study underscores promise nanotechnology‐enhanced immunotherapy developing nanovaccines against

Язык: Английский

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Dendritic Cell-Based Glioblastoma Vaccines: Advances and Challenges

IntechOpen eBooks, Год журнала: 2025, Номер unknown

Опубликована: Фев. 14, 2025

Glioblastoma (GBM) is the most aggressive malignancy of central nervous system. Despite advances in standard treatments such as surgery, radiotherapy, and chemotherapy, patients have a very poor prognosis. Tumor vaccines based on dendritic cells (DCs) provide promising new approach for GBM treatment. DCs, effective antigen-presenting cells, initiate adaptive immune responses by activating tumor-specific T cells. However, immunosuppressive microenvironment (characterized regulatory myeloid suppressor factors) physical barrier blood-brain (BBB) greatly limit efficacy DC vaccines. This chapter explores biological basis, preparation process, clinical progress, challenges, future directions DC-based Key aspects antigen selection, vitro culture activation, loading, delivery strategies are analyzed detail. Early trials demonstrated safety potential vaccines, while combination therapies reprogramming being used to overcome existing obstacles. precision personalization highlight their focus immunotherapy research. We believe that with continuous advancement technology interdisciplinary collaboration, can significantly improve survival rate quality life patients.

Язык: Английский

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