A tetravalent nanovaccine that inhibits growth of HPV-associated head and neck carcinoma via dendritic and T cell activation

Josi, Romano; Speiser, Daniel E.; de Brot, Simone; Vogt, Anne-Cathrine; Sevick-Muraca, Eva M.; Tolstonog, Genrich V.; Bachmann, Martin F.; Mohsen, Mona O.

doi:10.1016/j.isci.2024.109439

Cited by 2 publications

(2 citation statements)

References 42 publications

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“…Therefore, neoantigens, not expected to induce T cell tolerance, have attracted attention. Personalized vaccines directed against individual tumor neoantigens, using long peptides or RNA, have shown promising outcomes in mice [11] and humans [12,13]. However, challenges in this approach include identifying individual antigens, rendering epitopes immunogenic in humans, and the substantial tissue required for characterizing the immunopeptidome [14].…”

Section: Introductionmentioning

confidence: 99%

“…In addition to being used and sold as part of preventative vaccinations against the hepatitis B virus (HBV) and human papillomavirus (HPV), VLPs are currently being extensively studied in the area of cancer immunotherapy [26]. Among others, we have successfully designed and developed different therapeutic cancer vaccines utilizing VLPs and have provided several proofs of concepts in mice [11,[27][28][29]. Recently, we have focused on local delivery of VLPs as effective immunotherapy [29].…”

Section: Introductionmentioning

confidence: 99%

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Intranodal Injection of Immune Activator Demonstrates Antitumor Efficacy in an Adjuvant Approach

Josi,

Ogrina,

Rothen

et al. 2024

Vaccines

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The tumor-draining lymph nodes (tdLN) are the initial site of metastases and are the prime site for generating robust antitumor responses. In this study, we explored the efficacy of a universal immune activator (ImmAct) targeted to the tdLN. This approach can be viewed as an attempt to turn a cold, unresponsive tdLN into a hot, responsive site. The adjuvant antitumor efficacy of our novel intranodal injection was evaluated in an aggressive metastatic mammary carcinoma murine model. The cancer cells were inoculated subcutaneously in the lower quadrant of the mouse to provoke the tdLN (inguinal lymph node). The study encompasses a range of methodologies, including in vivo and in vitro assays and high-dimensional flow cytometry analysis. Our findings demonstrated that intranodal administration of ImmAct following the dissection of the primary tumor led to improved tumor-free survival and minimized weight loss. ImmAct led to both local and systemic alterations in the cellular and humoral immunity. Additionally, after ImmAct treatment, non-responders showed a higher rate of exhausted CD8+ T cells compared to responders. Indeed, our innovative approach surpassed the gold standard surgery of sentinel lymph node excision. Overall, intranodal administration of ImmAct yielded a robust antitumor immune response, offering protection against micrometastases and relapse.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Intranodal Injection of Immune Activator Demonstrates Antitumor Efficacy in an Adjuvant Approach

Josi,

Ogrina,

Rothen

et al. 2024

Vaccines

Self Cite

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Green Routes: Exploring Protein-Based Virus-like Nanoparticle Transport and Immune Activation in Nicotiana benthamiana for Biotechnological Applications

Josi,

Pardini,

Haindrich

et al. 2024

Vaccines

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Viral, bacterial, fungal, and nematode infections cause significant agricultural losses, with limited treatment options, necessitating novel approaches to enhance plant defense systems and protection against pathogens. Virus-like nanoparticles (VLPs), extensively used in animal and human therapies (e.g., vaccines and immune enhancers), hold potential for novel agricultural solutions and advancing plant nanotechnology. This study employed various methodologies, including VLP production, confocal microscopy, and real-time qPCR. Our findings demonstrated the presence of 30 nm Qβ-VLPs, fluorescently labeled, within the intercellular space of Nicotiana benthamiana leaves one hour post-infiltration. Furthermore, infiltration with Qβ-VLPs led to an upregulation of key defense genes (NbPR1a, NbPR5, NbNPR, NbERF1, NbMYC2, and NbLRR2) in treated plants. Using RT-qPCR, a significant increase in the relative expression levels of defense genes was observed, with sustained high levels of NbERF1 and NbLRR2 even after 24 h. These findings suggest that Qβ-VLPs effectively upregulate genes crucial for pathogen defense in N. benthamiana, initiating PAMP-triggered immunity and launching signaling cascades that enhance defense mechanisms. This innovative application of VLPs to activate plant defense programs advances plant nanobiotechnology, offering new agricultural solutions.

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A tetravalent nanovaccine that inhibits growth of HPV-associated head and neck carcinoma via dendritic and T cell activation

Cited by 2 publications

References 42 publications

Intranodal Injection of Immune Activator Demonstrates Antitumor Efficacy in an Adjuvant Approach

Intranodal Injection of Immune Activator Demonstrates Antitumor Efficacy in an Adjuvant Approach

Green Routes: Exploring Protein-Based Virus-like Nanoparticle Transport and Immune Activation in Nicotiana benthamiana for Biotechnological Applications

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