Reprogramming the genome of M13 bacteriophage for all-in-one personalized cancer vaccine DOI Open Access
Shengnan Huang,

Yanpu He,

Allison Madow

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 23, 2024

Abstract Peptide-based vaccines face limitations in immunogenicity and stability, challenges co-delivering antigens adjuvants effectively. Virus-based nanoparticles, particularly M13 bacteriophage, present a promising solution due to their genetic modifiability, intrinsic adjuvanticity, efficient antigen presentation capabilities. Here we developed programmable phage-based personalized cancer vaccine enabling single-step antigen-adjuvant assembly. Specifically, designed reprogrammed (RP) phage platform that precisely regulates Toll-like receptor 9 activation by programming its genome sequence modulates density through engineering. Vaccination studies with RP phages demonstrated the immune response could be modulated fine-tuning adjuvanticity density, revealing an optimal dose for maximum efficacy. The induced remarkable 24-fold increase neoantigen-specific CD8 + T cells eradicated established MC-38 tumors when combined anti-PD-1 therapy. These findings highlight phage’s potential as powerful nanovaccine vaccines.

Language: Английский

A Comprehensive Review on Phage Therapy and Phage-Based Drug Development DOI Creative Commons
Longzhu Cui, Shinya Watanabe, Kazuhiko Miyanaga

et al.

Antibiotics, Journal Year: 2024, Volume and Issue: 13(9), P. 870 - 870

Published: Sept. 11, 2024

Phage therapy, the use of bacteriophages (phages) to treat bacterial infections, is regaining momentum as a promising weapon against rising threat multidrug-resistant (MDR) bacteria. This comprehensive review explores historical context, modern resurgence phage and phage-facilitated advancements in medical technological fields. It details mechanisms action applications phages treating MDR particularly those associated with biofilms intracellular pathogens. The further highlights innovative uses vaccine development, cancer gene delivery vectors. Despite its targeted efficient approach, therapy faces challenges related stability, immune response, regulatory approval. By examining these areas detail, this underscores immense potential remaining hurdles integrating phage-based therapies into practices.

Language: Английский

Citations

16
Components, Formulations, Deliveries, and Combinations of Tumor Vaccines DOI
Tengfei Liu,

Wenyan Yao,

Wenyu Sun

et al.

ACS Nano, Journal Year: 2024, Volume and Issue: 18(29), P. 18801 - 18833

Published: July 9, 2024

Tumor vaccines, an important part of immunotherapy, prevent cancer or kill existing tumor cells by activating restoring the body's own immune system. Currently, various formulations vaccines have been developed, including cell membrane DNA mRNA polypeptide virus-vectored and tumor-in-situ vaccines. There are also multiple delivery systems for such as liposomes, vesicles, viruses, exosomes, emulsions. In addition, to decrease risk escape tolerance that may exist with a single vaccine, combination therapy radiotherapy, chemotherapy, checkpoint inhibitors, cytokines, CAR-T therapy, photoimmunotherapy is effective strategy. Given critical role in here, we look back history discuss antigens, adjuvants, formulations, systems, mechanisms, future directions

Language: Английский

Citations

10
Harnessing phytochemicals: innovative strategies to enhance cancer immunotherapy DOI Creative Commons
Qianru Zhu, Ruonan Zhang, Min Jin Ha

et al.

Drug Resistance Updates, Journal Year: 2025, Volume and Issue: 79, P. 101206 - 101206

Published: Feb. 1, 2025

Cancer immunotherapy has revolutionized cancer treatment, but therapeutic ineffectiveness-driven by the tumor microenvironment and immune evasion mechanisms-continues to limit its clinical efficacy. This challenge underscores need explore innovative approaches, such as multimodal immunotherapy. Phytochemicals, bioactive compounds derived from plants, have emerged promising candidates for overcoming these barriers due their immunomodulatory antitumor properties. review explores synergistic potential of phytochemicals in enhancing modulating responses, reprogramming microenvironment, reducing immunosuppressive factors. Integrating with conventional strategies represents a novel approach mitigating resistance outcomes. For instance, nab-paclitaxel shown checkpoint inhibitors, while QS-21 synergistically enhances efficacy vaccines. Furthermore, we highlight recent advancements leveraging nanotechnology engineer improved bioavailability targeted delivery. These innovations hold great promise optimizing application phytochemicals. However, further large-scale studies are crucial fully integrate into immunotherapeutic regimens effectively.

Language: Английский

Citations

1
Storable Polydopamine Nanoparticles Combined with Bacillus Calmette‐Guérin for Photothermal‐Immunotherapy of Colorectal Cancer DOI

Ze‐Nan Zhuang,

Yong‐Dan Qi,

Qian‐Xiao Huang

et al.

Advanced Functional Materials, Journal Year: 2024, Volume and Issue: unknown

Published: July 30, 2024

Abstract Photothermal immunotherapy emerges as a promising strategy for treating tumors. However, the majority of current photothermal approaches do not yet show significant potential clinical translation. In this study, lyophilized polydopamine (PDA) nanoparticles combined with Bacillus Calmette–Guérin (BCG) are investigated against colorectal cancer. By simply mixing two powders, PDA can covalently bond onto BCG to form BCG@PDA. This combination demonstrates potent cytotoxic effect on tumor cells by utilizing nanoparticles. addition, heightened immune response triggered vaccine, evidenced secretion important pro‐inflammatory cytokines and activation antigen‐presenting cells, is observed. vivo testing murine colon cancer model that treatment significantly inhibits growth. Further, be stored at −20 °C up 1 year stable properties. Therefore, study only presents reliable method storing therapeutic but also application BCG@PDA in

Language: Английский

Citations

4
An Injectable Gambogic Acid Loaded Nanocomposite Hydrogel Enhances Antitumor Effect by Reshaping Immunosuppressive Tumor Microenvironment DOI

Dan Lei,

Wanru Wang,

Jianhang Zhao

et al.

Published: Jan. 1, 2025

Language: Английский

Citations

0
Tumor-Targeted Delivery of PD-1-Displaying Bacteriophages by Escherichia coli for Adjuvant Treatment of Colorectal Cancer DOI
Hongrui Li, Ying Zhou, Bang‐Ce Ye

et al.

ACS Synthetic Biology, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 10, 2025

Bacteriophages, leveraging phage display and chemical modification, have the potential to deliver large payloads of antitumor agents with precision advance vaccine development. However, systemic administration often induces neutralizing antibodies, which accelerate clearance reduce accumulation at target site. To address this limitation, we propose a genetically modified nonpathogenic bacterial strain that specifically targets tumors releases programmed death ligand 1 (PD-L1)-specific M13 bacteriophage within tumor tissue. We assessed efficacy phage-expressing as an adjunctive therapeutic strategy along engineered for controlled release immunotoxin. The combination these strains demonstrated synergistic effects in eliciting immune responses inhibiting growth murine model colorectal cancer (CRC). Moreover, when combined Folfox, significantly extended survival. This vivo expression tumor-specific mediated by provides effective safe method targeted delivery tumors.

Language: Английский

Citations

0
Bifunctional Phage Particles Augment CD40 Activation and Enhance Lymph Node-Targeted Delivery of Personalized Neoantigen Vaccines DOI
Xiaotong Chen, Lei Lei,

Jiayao Yan

et al.

ACS Nano, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 11, 2025

Although personalized neoantigen cancer vaccines have emerged as a promising strategy for treatment, challenges remain to develop immune-stimulatory carriers which allow simultaneous transport of adjuvants and lymph nodes (LNs). With inherent immunogenicity, genetic plasticity, efficiency large-scale production, M13 phages represent an attractive platform vaccine delivery natural bionanomaterials. Here, we report the discovery anti-CD40 designed ankyrin repeat protein (DARPin) propose bifunctional ph age based on this DARPin (M13CD40). M13CD40-based show improved accumulation prolonged antigen retention in LNs compared with nontargeting phage due abundance CD40-positive cells LNs. Besides intrinsic immunogenicity phages, also benefit from additional CD40 stimulation multiple copies DARPins displayed M13CD40 phages. Subcutaneous immunization results more robust antigen-specific immune responses superior antitumor efficacy poorly immunogenic tumor models vaccines. Combination therapy PD-1 blockade further enhances T cell cytotoxicity improves control. To summarize, our findings highlight nanoagonist well efficient vehicle LN-targeted

Language: Английский

Citations

0
An Injectable Gambogic Acid Loaded Nanocomposite Hydrogel Enhances Antitumor Effect by Reshaping Immunosuppressive Tumor Microenvironment DOI Creative Commons

Dan Lei,

Wanru Wang,

Jianhang Zhao

et al.

Materials Today Bio, Journal Year: 2025, Volume and Issue: 31, P. 101611 - 101611

Published: Feb. 24, 2025

Language: Английский

Citations

0
In situ carrier-free nanovaccines reversing the immunosuppressive microenvironment for boosting tumor immunotherapy DOI
Yi‐Lei Zhao,

Guoxin Zhu,

Xuechun Wang

et al.

Chinese Chemical Letters, Journal Year: 2025, Volume and Issue: unknown, P. 111031 - 111031

Published: March 1, 2025

Language: Английский

Citations

0
Permanent Efferocytosis Prevention by Terminating MerTK Recycle on Tumor-Associated Macrophages for Cancer Immunotherapy DOI
Pei Huang, Yiwen Liu, Caiyan Zhao

et al.

Journal of the American Chemical Society, Journal Year: 2025, Volume and Issue: unknown

Published: April 28, 2025

Efferocytosis of apoptotic tumor cells by tumor-associated macrophages mediated through the phosphatidylserine (PtdSer)/MER proto-oncogene tyrosine kinase (MerTK) axis can exacerbate immunosuppression, and conversely, prevention efferocytosis via blocking PtdSer-MerTK association using prevalent antibodies represents a promising strategy for reversing immunosuppression boosting antitumor immunity. However, it remains unclear whether antibody blockade induce durable achieve sustained growth inhibition. Here, we have shown that utilizing PtdSer MerTK induced only transient rather than persistent effect, little enhancement was observed even after improving enrichment in sites. Further mechanistic studies suggested degradation anti-MerTK recycling receptor to cell membrane would compromise therapeutic benefits blockade. Based on these findings, developed CRISPR/Cas9 gene editing system deployed Cas9 mRNA sgRNA permanently knock out MerTK, which achieved prevention, elicited situ vaccination immune responses enhancing X-ray irradiation-induced immunogenic death, led suppression effects together with anti-PtdSer irradiation treatment multiple B16 melanoma models. Our findings provide reliable gene-editing-mediated long-term modulating homeostasis overcoming MerTK-dependent cancer evasion, generating adaptive immunotherapy.

Language: Английский

Citations

0