Cancer vaccines are promising therapeutic approaches to enhance specific T-cell immunity against most solid tumors. By stimulating anti-tumor immunity, clearing minimal residual disease, and minimizing adverse effects, these vaccines target tumor cells and are effective when combined with immune checkpoint blockade or other immunotherapies. However, the development of tumor cell-based vaccines faces quality issues due to poor immunogenicity, tumor heterogeneity, a suppressive tumor immune microenvironment, and ineffective delivery methods. In contrast, extracellular vesicles (EVs), naturally released by cells, are considered the ideal drug carriers and vaccine platforms. EVs offer highly organ-specific targeting, induce broader and more effective immune responses, and demonstrate superior tissue delivery ability. The development of EV vaccines is crucial for advancing cancer immunotherapy. Compared to cell-based vaccines, EV vaccines produced under Good Manufacturing Practices (GMP) offer advantages such as high safety, ease of preservation and transport, and a wide range of sources. This review summarizes the latest research findings on EV vaccine and potential applications in this field. It also highlights novel neoantigens for the development of EV vaccines against cancer.

01 Dec 2024·Journal of Controlled Release

Enhancing preventive and therapeutic cancer vaccine efficacy through biotherapeutic ligand-associated extracellular vesicles

Article

Author: Gursel, Arda ; Larssen, Pia ; Gursel, Ihsan ; Eldh, Maria ; Gursel, Mayda ; Guler, Ulku ; Yildirim, Tugce Canavar ; Salih, Bekir ; Horuluoglu, Begum Han ; Yagci, Fuat C ; Ayanoglu, Ihsan Cihan ; Gabrielsson, Susanne ; Akpinar, Gozde Gucluler ; Yildirim, Muzaffer ; Yazar, Volkan ; Bayyurt-Kocabas, Banu ; Evcili, Irem ; Kahraman, Tamer ; Yilmaz, Ismail C

Extracellular vesicles (EVs), secreted by almost all living cells, have gained significant attention for their role in intercellular communication and their potential as versatile carriers for biotherapeutics. However, the clinical translation of EV-based therapies faces significant challenges, primarily due to the lack of efficient methods for loading biotherapeutic agents into EVs. This study introduces a simple, reproducible strategy for the simultaneous incorporation of various biotherapeutics within EVs. The process is gentle and preserves the essential physicochemical and biological characteristics of EVs, thereby protecting labile ligands from premature degradation and elimination. The binding and uptake efficiency of EVs by target cells reached approximately 97 % within 24 h of incubation. Administration of EVs loaded with oligodeoxynucleotides (ODN) resulted in a 4-fold increase in IFNγ⁺ CD4⁺ T cells and a 5-fold increase in IFNγ⁺ CD8⁺ T cells in the spleens and lymph nodes. Additionally, the co-administration of EVs with ODN and ovalbumin (OVA) induced elevated Th1-biased antibody responses and antigen-specific cytotoxic T-cell responses, providing long-lasting complete protection in 60 % of mice against T-cell thymoma challenge. Furthermore, EVs associated with three different ligands (OVA, CpG-ODN, and α-GalCer) effectively regressed established murine melanoma and significantly improved survival rates in mice. This study presents a powerful and promising approach to overcoming the limitations of EV-based cancer vaccines, advancing the development of effective cancer immunotherapies. SUMMARY: Immunization with EVs that are co-associated with antigen and biotherapeutic cargo through a lyophilization-based technique elicits potent anti-cancer immunity.

01 Jan 2016·Vaccine Design

Assessment of Live Plague Vaccine Candidates

Article

Author: Feodorova, Valentina A ; Sayapina, Lidiya V ; Motin, Vladimir L

Since its creation in the early twentieth century, live plague vaccine EV has been successfully applied to millions of people without severe complications. This vaccine has been proven to elicit protection against both bubonic and pneumonic plague, and it is still in use in populations at risk mainly in the countries of the former Soviet Union. Despite extensive efforts in developing subunit vaccines, there is a reviving interest in creation of a precisely attenuated strain of Yersinia pestis superior to the EV that can serve as a live plague vaccine with improved characteristics. Here we summarize decades of experience of the Russian anti-plague research in developing a standard protocol for early-stage evaluation of safety and immunogenicity of live plague vaccines. This protocol allows step-by-step comparison of the novel test candidates with the EV vaccine by using subcutaneous immunization and bubonic plague infection models in two animal species, e.g., guinea pigs and mice.

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Indication	Highest Phase	Country/Location	Organization	Date
Neoplasms	Preclinical	DK	Evaxion Biotech A/S	24 Jan 2024

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