Intratumoral delivered novel circular mRNA encoding cytokines for immune modulation and cancer therapy

Yang, Jiali; Zhu, Jiafeng; Sun, Jiejie; Chen, Yiyun; Du, Yaran; Tan, Yiling; Wu, Linpeng; Zhai, Mengting; Wei, Lixiang; Li, Na; Hou, Qiangbo; Tong, Zhenbo; Bechthold, Andreas; Tian, Hao; Sun, Zhenhua; Zuo, Chijian

doi:10.1016/j.omtn.2022.09.010

Cited by 20 publications

(17 citation statements)

References 36 publications

(34 reference statements)

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“…Thus, we aimed to select an IRES to optimize the protein expression of circRNA in mouse muscle tissues. Previous studies have provided some clues, CVB3-IRES, EV29-IRES, EV33-IRES, and VICP-IRES directed translation more efficiently than the commonly used EMCV-IRES in specific tissues and cells 31 , 34 , 35 . These four IRES elements mentioned above were tested in vitro and in vivo .…”

Section: Resultsmentioning

confidence: 99%

“…As IRES-mediated translation is dependent on the availability of IRES trans-acting factors, which vary among cell and tissue types, different IRES elements or even the same IRES element initiate distinct translation efficiency 31 , 34 , 35 . Thus, we aimed to select an IRES to optimize the protein expression of circRNA in mouse muscle tissues.…”

Section: Resultsmentioning

confidence: 99%

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Circular RNA cancer vaccines drive immunity in hard-to-treat malignancies

Li¹,

Peng²,

Yang³

et al. 2022

Theranostics

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Rationale: Messenger RNA (mRNA) vaccine outperforms other kinds of cancer immunotherapy due to its high response rates, easy preparation, and wide applicability, which is considered as one of the most promising forms of next-generation cancer therapies. However, the inherent instability and insufficient protein expression duration of mRNA limit the efficacy and widespread application of the vaccine. Methods: Here, we first tested the possibility of a novel circular RNA (circRNA) platform for protein expression and compare its duration with linear RNA. Then, we developed a lipid nanoparticle (LNP) system for circRNA delivery in vitro and in vivo . Next, the innate and adaptive immune response of circRNA-LNP complex was evaluated in vivo . The anti-tumor efficacy of circRNA-LNP was further confirmed in three tumor models. Finally, the possibility of combination therapy with circRNA-LNP and adoptive cell transfer therapy was further investigated in a late-stage tumor model. Results: We successfully increased the stability of the RNA vaccine by circularizing the linear RNA molecules to form highly stable circRNA molecules which exhibited durable protein expression ability. By encapsulating the antigen-coding circRNA in LNP enabling in vivo expression, we established a novel circRNA vaccine platform, which was capable of triggering robust innate and adaptive immune activation and showed superior anti-tumor efficacy in multiple mouse tumor models. Conclusions: Overall, our circRNA vaccine platform provides a novel prospect for the development of cancer RNA vaccines in a wide range of hard-to-treat malignancies.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Circular RNA cancer vaccines drive immunity in hard-to-treat malignancies

Li¹,

Peng²,

Yang³

et al. 2022

Theranostics

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“…Recently, intratumoral administration of naked circular mRNA (cmRNA) encoding cytokines dissolved in PBS into B16F10 syngeneic tumors in mice showed that cmRNA was delivered and expressed in the tumor tissue. [ 185 ] This resulted in modulating the antitumor immune responses to elicit the anti‐PD‐1 antibody induced tumor repression in mouse model. [ 185 ]…”

Section: Methods For Delivering Mrna Vaccinementioning

confidence: 99%

“…[ 185 ] This resulted in modulating the antitumor immune responses to elicit the anti‐PD‐1 antibody induced tumor repression in mouse model. [ 185 ]…”

Section: Methods For Delivering Mrna Vaccinementioning

confidence: 99%

Advancing Cancer Immunotherapy: The Potential of mRNA Vaccines As a Promising Therapeutic Approach

Goyal,

Chattopadhyay,

Navik

et al. 2023

Advanced Therapeutics

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AbstractmRNA vaccines have long been recognized for their ability to induce robust immune responses. The discovery that mRNA vaccines may also contribute to anti‐tumor immunity has made them a promising therapeutic approach against cancer. Recent advances in understanding of immune system have been precious in developing therapeutic strategies that target pathways involved in tumor survival and progression, leading to the most reliable therapeutic strategies in cancer treatment history. Among all traditional cancer treatments, cancer immunotherapies are less toxic and more effective, even in advanced or recurrent stages of cancer. Recent advancements in genomics and machine learning algorithms give new insight into vaccine development. mRNA vaccines are designed to interfere with STING and TLR pathways, activating more CD8+ T‐cells involved in destroying tumor cells and inhibiting tumor growth. A stronger immune response can be achieved by incorporating immunological adjuvants alongside mRNA. Non‐formulated or vehicle‐based mRNA vaccines, when combined with adjuvants, efficiently express tumor antigens through antigen‐presenting cells and stimulate both innate and adaptive immune responses. Co‐delivery with additional immunotherapeutic agents, such as checkpoint inhibitors, further enhances the efficacy of mRNA vaccines. This article focused on the current clinical approaches and challenges to consider when developing mRNA‐based vaccine technology for cancer treatment.This article is protected by copyright. All rights reserved

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“…Since then, numerous preclinical and clinical studies have demonstrated the capability and possibilities of mRNA vaccines to combat against cancer (Table 1). The commonly used clinical methods of mRNA cancer vaccine include direct injection of mRNA vaccine, [170,171] transfection of antigen-presenting cells, [172,173] and mRNA encoding chimeric antigen receptor (CAR) (CARVac strategy), [174,175] etc.…”

Section: Cancer Immunotherapymentioning

confidence: 99%

Building a Better Silver Bullet: Current Status and Perspectives of Non‐Viral Vectors for mRNA Vaccines

Gu,

Xu,

Liu

et al. 2023

Adv Healthcare Materials

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In recent years, messenger RNA (mRNA) vaccines have exhibited great potential to replace conventional vaccines owing to their low risk of insertional mutagenesis, safety and efficacy, rapid and scalable production, and low‐cost manufacturing. With the great achievements of chemical modification and sequence optimization methods of mRNA, the key to the success of mRNA vaccines is strictly dependent on safe and efficient gene vectors. Among various delivery platforms, non‐viral mRNA vectors could represent perfect choices for future clinical translation regarding their safety, sufficient packaging capability, low immunogenicity, and versatility. In this review, the recent progress in the development of non‐viral mRNA vectors is focused on. Various organic vectors including lipid nanoparticles (LNPs), polymers, peptides, and exosomes for efficient mRNA delivery are presented and summarized. Furthermore, the latest advances in clinical trials of mRNA vaccines are described. Finally, the current challenges and future possibilities for the clinical translation of these promising mRNA vectors are also discussed.

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Intratumoral delivered novel circular mRNA encoding cytokines for immune modulation and cancer therapy

Cited by 20 publications

References 36 publications

Circular RNA cancer vaccines drive immunity in hard-to-treat malignancies

Circular RNA cancer vaccines drive immunity in hard-to-treat malignancies

Advancing Cancer Immunotherapy: The Potential of mRNA Vaccines As a Promising Therapeutic Approach

Building a Better Silver Bullet: Current Status and Perspectives of Non‐Viral Vectors for mRNA Vaccines

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