mRNA vaccines for cancer immunotherapy

Vishweshwaraiah, Yashavantha; Dokholyan, Nikolay V.

doi:10.3389/fimmu.2022.1029069

Cited by 72 publications

(41 citation statements)

References 93 publications

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“…(2) Unlike DNA vaccines, mRNA vaccines cannot be integrated into genomic sequences and therefore have no insertional mutations . Transient expression of mRNA-encoded antigens allows better control of antigen exposure and reduces the risk of long-term antigen exposure . In 1990, the successful expression of transfected IVT mRNA in mouse skeletal muscle cells provided the possibility for the transformation of IVT mRNA into an anti avian influenza vaccine .…”

Section: Definition Composition and Classification Of Cancer Vaccinesmentioning

confidence: 99%

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Advances in Cancer Vaccine Research

Liu,

Xiao,

Zhang

et al. 2023

ACS Biomater. Sci. Eng.

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The use of cancer vaccines is considered a promising therapeutic strategy in clinical oncology, which is achieved by stimulating antitumor immunity with tumor antigens delivered in the form of cells, peptides, viruses, and nucleic acids. The ideal cancer vaccine has many advantages, including low toxicity, specificity, and induction of persistent immune memory to overcome tumor heterogeneity and reverse the immunosuppressive microenvironment. Many therapeutic vaccines have entered clinical trials for a variety of cancers, including melanoma, breast cancer, lung cancer, and others. However, many challenges, including single antigen targeting, weak immunogenicity, off-target effects, and impaired immune response, have hindered their broad clinical translation. In this review, we introduce the principle of action, components (including antigens and adjuvants), and classification (according to applicable objects and preparation methods) of cancer vaccines, summarize the delivery methods of cancer vaccines, and review the clinical and theoretical research progress of cancer vaccines. We also present new insights into cancer vaccine technologies, platforms, and applications as well as an understanding of potential next-generation preventive and therapeutic vaccine technologies, providing a broader perspective for future vaccine design.

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Section: Definition Composition and Classification Of Cancer Vaccinesmentioning

confidence: 99%

“…91 Depending on their preparation methods, they can be classified as follows: cell-based cancer vaccines, viral-based cancer vaccines, peptide-based cancer vaccines, and genetic vaccines (Figure 3). 92 2.3.3. Cell-Based Cancer Vaccines.…”

Section: Preventive Cancer Vaccinementioning

confidence: 99%

Advances in Cancer Vaccine Research

Liu,

Xiao,

Zhang

et al. 2023

ACS Biomater. Sci. Eng.

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“…5 While there are many types of cancer vaccines, mRNA-based vaccines have recently attracted widespread interest because of their rapid development during the COVID-19 pandemic. 6 Like the COVID-19 vaccines, the main purpose of an mRNA cancer vaccine is to train the body to recognize and destroy cancer via the translation of mRNA into protein antigens. In a cancer vaccine, mRNA encoding a specific tumor antigen is delivered to specialized immune cells called antigen presenting cells (APCs).…”

Section: Introductionmentioning

confidence: 99%

“…9 Additionally, mRNA is rapidly degraded in the cytoplasm which results in transient antigen presentation and avoids prolonged activation of the immune system. 6 With regard to delivery, mRNA only needs to be delivered into the cytoplasm while DNA vaccines need to be delivered into the nucleus. 10 Furthermore, the worldwide deployment of COVID-19 vaccines led to the development of good manufacturing practice (GMP) protocols to rapidly produce mRNA vaccines.…”

Section: Introductionmentioning

confidence: 99%

“… From a safety perspective, mRNA vaccines are advantageous because mRNA does not integrate into the host genome so there is no risk of insertional mutagenesis . Additionally, mRNA is rapidly degraded in the cytoplasm which results in transient antigen presentation and avoids prolonged activation of the immune system . With regard to delivery, mRNA only needs to be delivered into the cytoplasm while DNA vaccines need to be delivered into the nucleus .…”

Section: Introductionmentioning

confidence: 99%

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Advances in Nonviral mRNA Delivery Materials and Their Application as Vaccines for Melanoma Therapy

Neill,

Romero,

Fenton

2023

ACS Appl. Bio Mater.

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Messenger RNA (mRNA) vaccines are promising platforms for cancer immunotherapy because of their potential to encode for a variety of tumor antigens, high tolerability, and capacity to induce strong antitumor immune responses. However, the clinical translation of mRNA cancer vaccines can be hindered by the inefficient delivery of mRNA in vivo. In this review, we provide an overview of mRNA cancer vaccines by discussing their utility in treating melanoma. Specifically, we begin our review by describing the barriers that can impede mRNA delivery to target cells. We then review native mRNA structure and discuss various modification methods shown to enhance mRNA stability and transfection. Next, we outline the advantages and challenges of three nonviral carrier platforms (lipid nanoparticles, polymeric nanoparticles, and lipopolyplexes) frequently used for mRNA delivery. Last, we summarize preclinical and clinical studies that have investigated nonviral mRNA vaccines for the treatment of melanoma. In writing this review, we aim to highlight innovative nonviral strategies designed to address mRNA delivery challenges while emphasizing the exciting potential of mRNA vaccines as next-generation therapies for the treatment of cancers.

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Delivery of mRNA Vaccine with 1, 2‐Diesters‐Derived Lipids Elicits Fast Liver Clearance for Safe and Effective Cancer Immunotherapy

Xu,

Hu,

Xia

et al. 2023

Adv Healthcare Materials

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Messenger RNA (mRNA) vaccine is explored as a promising strategy for cancer immunotherapy, but the side effects, especially the liver‐related damage caused by LNP, raise concerns about its safety. In this study, a novel library of 248 ionizable lipids comprising 1,2‐diesters is designed via a two‐step process involving the epoxide ring‐opening reaction with carboxyl group‐containing alkyl chains followed by an esterification reaction with the tertiary amines. Owing to the special chemical structure of 1,2‐diesters, the top‐performing lipids and formulations exhibit a faster clearance rate in the liver, contributing to increased stability and higher safety compared with DLin‐MC3‐DMA. Moreover, the LNP shows superior intramuscular mRNA delivery and elicits robust antigen‐specific immune activation. The vaccinations delivered by the LNP system suppress tumor growth and prolong survival in both model human papillomavirus E7 and ovalbumin antigen‐expressing tumor models. Finally, the structure of lipids which enhances the protein expression in the spleen and draining lymph nodes compared with ALC‐0315 lipid in Comirnaty is further optimized. In conclusion, the 1, 2‐diester‐derived lipids exhibit rapid liver clearance and effective anticancer efficiency to different types of antigens‐expressing tumor models, which may be a safe and universal platform for mRNA vaccines.

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mRNA vaccines for cancer immunotherapy

Cited by 72 publications

References 93 publications

Advances in Cancer Vaccine Research

Advances in Cancer Vaccine Research

Advances in Nonviral mRNA Delivery Materials and Their Application as Vaccines for Melanoma Therapy

Delivery of mRNA Vaccine with 1, 2‐Diesters‐Derived Lipids Elicits Fast Liver Clearance for Safe and Effective Cancer Immunotherapy

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