Safety and immunogenicity of an optimized self-replicating RNA platform for low dose or single dose vaccine applications: a randomized, open label Phase I study in healthy volunteers DOI Creative Commons
Christian J. Maine, Shigeki J. Miyake-Stoner, Darina Spasova

et al.

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: Jan. 7, 2025

Self-replicating RNA (srRNA) technology, in comparison to mRNA vaccines, has shown dose-sparing by approximately 10-fold and more durable immune responses. However, no improvements are observed the adverse events profile. Here, we develop an srRNA vaccine platform with optimized non-coding regions demonstrate immunogenicity safety preclinical clinical development. Optimized vaccines generate protective immunity (according WHO defined thresholds) at doses up 1,000,000-fold lower than female mouse models of influenza rabies. Clinically, RBI-4000, vector encoding rabies glycoprotein, was evaluated a Phase I study (NCT06048770). RBI-4000 able elicit de novo majority healthy participants when administered dose 0.1, 1, or 10 microgram (71%, 94%, 100%, respectively) prime-boost schedule. Similarly, observe above benchmark protection following single administration most both 1 doses. There serious reported across all cohorts. These data establish high therapeutic index vectors, demonstrating feasibility low approaches for applications. Here authors report self-replicating approach that generates much mice. In using glycoprotein as antigen, they show robust responses 0.1 µg, favorable

Language: Английский

RNA vaccines for cancer: Principles to practice DOI
Pablo Guasp, Charlotte Reiche, Zachary Sethna

et al.

Cancer Cell, Journal Year: 2024, Volume and Issue: 42(7), P. 1163 - 1184

Published: June 6, 2024

Language: Английский

Citations

18
A neoantigen vaccine generates antitumour immunity in renal cell carcinoma DOI Creative Commons
David A. Braun,

Giorgia Moranzoni,

Vipheaviny Chea

et al.

Nature, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 5, 2025

Personalized cancer vaccines (PCVs) can generate circulating immune responses against predicted neoantigens1–6. However, whether such target driver mutations, lead to recognition of a patient's tumour and result in clinical activity are largely unknown. These questions particular interest for patients who have tumours with low mutational burden. Here we conducted phase I trial (ClinicalTrials.gov identifier NCT02950766) test neoantigen-targeting PCV high-risk, fully resected clear cell renal carcinoma (RCC; stage III or IV) without ipilimumab administered adjacent the vaccine. At median follow-up 40.2 months after surgery, none 9 participants enrolled study had recurrence RCC. No dose-limiting toxicities were observed. All generated T antigens, including RCC mutations VHL, PBRM1, BAP1, KDM5C PIK3CA. Following vaccination, there was durable expansion peripheral clones. Moreover, reactivity autologous detected seven out nine patients. Our results demonstrate that PCVs high-risk highly immunogenic, capable targeting key induce antitumour immunity. observations, conjunction absence all vaccinated patients, highlights promise as effective adjuvant therapy A personalized vaccine led polyfunctional recognition, associated no carcinoma.

Language: Английский

Citations

14
Present and future of cancer nano-immunotherapy: opportunities, obstacles and challenges DOI Creative Commons
Man Wang, Fei Yu, Yuan Zhang

et al.

Molecular Cancer, Journal Year: 2025, Volume and Issue: 24(1)

Published: Jan. 18, 2025

Clinically, multimodal therapies are adopted worldwide for the management of cancer, which continues to be a leading cause death. In recent years, immunotherapy has firmly established itself as new paradigm in cancer care that activates body's immune defense cope with cancer. Immunotherapy resulted significant breakthroughs treatment stubborn tumors, dramatically improving clinical outcome patients. Multiple forms immunotherapy, including checkpoint inhibitors (ICIs), adoptive cell therapy and vaccines, have become widely available. However, effectiveness these immunotherapies is not much satisfying. Many patients do respond disease recurrence appears unavoidable because rapidly evolving resistance. Moreover, can give rise severe off-target immune-related adverse events. Strategies remove hindrances mainly focus on development combinatorial or exploitation novel immunotherapeutic mediations. Nanomaterials carrying anticancer agents target site considered practical approaches treatment. Nanomedicine combined offers possibility potentiate systemic antitumor immunity facilitate selective cytotoxicity against cells an effective safe manner. A myriad nano-enabled currently under investigation. Owing gaps between preclinical studies, nano-immunotherapy faces multiple challenges, biosafety nanomaterials trial design. this review, we provide overview summarize evidence indicating how nanomedicine-based increase efficacy immunotherapies. We also discuss key challenges emerged era nanotechnology-based immunotherapy. Taken together, combination drawing increasing attention, it anticipated will achieve desired success therapy.

Language: Английский

Citations

11
Clinical advances of mRNA vaccines for cancer immunotherapy DOI Creative Commons
Alexey V. Yaremenko, Muhammad Muzamil Khan,

Xueyan Zhen

et al.

Med, Journal Year: 2025, Volume and Issue: 6(1), P. 100562 - 100562

Published: Jan. 1, 2025

Language: Английский

Citations

8
Safety and immunogenicity of an optimized self-replicating RNA platform for low dose or single dose vaccine applications: a randomized, open label Phase I study in healthy volunteers DOI Creative Commons
Christian J. Maine, Shigeki J. Miyake-Stoner, Darina Spasova

et al.

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: Jan. 7, 2025

Self-replicating RNA (srRNA) technology, in comparison to mRNA vaccines, has shown dose-sparing by approximately 10-fold and more durable immune responses. However, no improvements are observed the adverse events profile. Here, we develop an srRNA vaccine platform with optimized non-coding regions demonstrate immunogenicity safety preclinical clinical development. Optimized vaccines generate protective immunity (according WHO defined thresholds) at doses up 1,000,000-fold lower than female mouse models of influenza rabies. Clinically, RBI-4000, vector encoding rabies glycoprotein, was evaluated a Phase I study (NCT06048770). RBI-4000 able elicit de novo majority healthy participants when administered dose 0.1, 1, or 10 microgram (71%, 94%, 100%, respectively) prime-boost schedule. Similarly, observe above benchmark protection following single administration most both 1 doses. There serious reported across all cohorts. These data establish high therapeutic index vectors, demonstrating feasibility low approaches for applications. Here authors report self-replicating approach that generates much mice. In using glycoprotein as antigen, they show robust responses 0.1 µg, favorable

Language: Английский

Citations

5