Comparison of DNA and mRNA vaccines against cancer

Highlights

• Cancer vaccines have a long history, but traditional protein/peptide antigens have not had much success.

• Nucleic acid vaccines based on either plasmid DNA or mRNA encoding tumor antigens are a promising alternative.

• The present review compares DNA and mRNA vaccines based on preparation, delivery, immunogenicity, and clinical trials.

• Other immunotherapies such as checkpoint inhibitors can be combined with NAVs.

Nucleic acid vaccines (NAVs) have recently been tested as a cancer therapy. DNA and mRNA vaccines deliver genetic information encoding tumor antigens (TAs) to the host, which then produces immune responses against cancer cells that express the TAs. Although NAVs are easy, safe, and simple to manufacture, they have not so far been considered viable alternatives to peptide vaccines. Choosing the right TAs, insufficient immunogenicity, and the immunosuppressive nature of cancer are some challenges to this approach. In this review, we discuss approaches that been used to improve the efficiency of anticancer NAVs.

Introduction

Cancer remains a challenging medical problem affecting millions of people around the world. Treatment strategies, such as surgery, chemotherapy, radiotherapy, and hormonal therapies, are applied alone or in combinations. More recently, targeted drugs and immunotherapy have gained research attention. Nevertheless, innovative cancer treatments are still being investigated in ever-increasing numbers [1]. The immune system has the potential to fight cancer and, thus, immunotherapy is designed to educate the immune system to identify and eliminate tumors; as a result, it has fewer adverse effects compared with chemotherapy [2]. Cancer immunotherapy strategies, such as cancer vaccines, bispecific antibodies, chimeric antigen receptors (CAR) T cells, checkpoint inhibitors, and other cell-based therapies, are important platforms 2, 3. Conventional vaccines based on live attenuated and inactivated pathogens, synthetic peptides, and recombinant subunit vaccines are widely used to prevent many infectious diseases. However, the manufacturing procedures of vaccines are not completely safe, and have a high risk of contamination with living pathogens. Therefore, the development of alternative vaccines is necessary for both infectious diseases and for non-infectious diseases, such as cancer 4, 5. Cancer vaccines have been studied for decades with some sporadic success, but have yet to penetrate the oncological mainstream. They include peptide vaccines, cell-based vaccines, viral vector vaccines, and NAVs. All these vaccines are designed to trigger or augment an immune response toward antigens expressed more or less specifically on tumor cells [6]. Among the different types of cancer vaccine tested, NAVs, such as DNA or mRNA vaccines, have been considered attractive because of their safe, simple, and rapid manufacturing process [7]. Cancer vaccines are more often used as a therapeutic approach, compared with infectious diseases, where prophylactic vaccines are more common. Cancer vaccines are designed to induce an immune response against tumor-derived antigens or TAs [8]. TAs can have a central role in tumor initiation, progression, and metastasis 6, 8. They can include tumor-associated antigens (TAAs) and tumor-specific antigens (TSAs). Oncofetal antigens, cancer-testis antigens (CTAs), and overexpressed self-antigens have been considered to be TAAs. CTAs and oncofetal antigens are considered to be good candidates for cancer immunotherapy because they display zero or low expression in normal adult somatic cells; moreover, they are shared by many cancerous tumors in different patients to various extents, and are also expressed in different pathological types of epithelial tumor [9]. By contrast, mutated self-antigens or TSAs/neoantigens require expensive and laborious identification in the tumors of individual patients, but have shown improved efficacy in clinical trials compared with TAAs. Generally speaking, TAAs have been more often studied than TSAs in NAVs used for cancer [10].

In this review, we discuss current approaches using NAVs for cancer, compare DNA and mRNA cancer vaccines (Box 1 provides an introduction to DNA and mRNA cancer vaccines), summarize the latest challenges and recent successes, and offer perspectives for the future application of NAVs in cancer therapy.