Introduction
For decades, how to treat cancer effectively has been explored and studied, and the progresses and breakthroughs in this field have changed the prospect of cancer treatment. At present, there are many treatment ways to choose from, such as surgical resection, chemotherapy, radiotherapy, hormone therapy and immunotherapy [1]. However, the inevitably side effects of these methods and the risk of tumor recurrence contributed to cure cancer difficultly. Cancer vaccine is an innovative type of vaccine, which reduces the side effects of traditional cancer treatment and improves the treatment compliance of cancer patients by strengthening the body’s natural defense against cancer. Although most cancer vaccines have not yet been mass-produced and widely used, there is no doubt that the treatment of cancer vaccine will be one of the most powerful cancer treatments in the future. The effective antigenic substances in cancer vaccines can be cancer cells, cell lysates, proteins, peptides, and nucleic acids that encode some cancer antigens [2]. In general, the immunogenicity of tumor antigens is poor, so it is not realistic to achieve the ideal tumor immune effect only by injecting tumor antigen.
Adding immune stimulants to the vaccine system as a way to stimulate the body’s innate immunity has been proved by years of researches on the prevention of viruses and bacteria [3]. When injecting adjuvants before antigens injection or simultaneously injecting adjuvants to bind to antigens, nonspecific immune response is enhanced or the type of immune response is reversed. The adjuvants continue to evolve, from aluminum and Freund’s adjuvants to lipopolysaccharide endotoxins, from gram-negative bacteria to various immunostimulatory complexes (ISCOM) [4]. The reasonable use of adjuvants can reduce antigenic applications, reduce the incidence of adverse reactions, thereby achieving better immune effects [5]. Successful vaccines should include three key components: an effective antigenic cargo, immunostimulatory agent, and a targeted delivery system that precise delivers antigens and immunostimulators to the appropriate site [6].
In the vaccine system, adjuvants can be divided into two roles, one is immune stimulant, the other is delivery carrier to exert immune effect. Because of its good safety, controllable size and easy functionalization, lipids can not only be used as immune stimulants (stimulate innate immunity), but also can be self-assembled into carriers for antigen delivery (delivery to some cells). It is considered be an excellent candidate for adjuvants, and the characteristics of lipid adjuvants provide a new prospect for the development of effective cancer vaccines. When lipid adjuvants are used in cancer vaccines, innate immune receptors are usually stimulated at once. After the innate immunity is activated, the affinity of T cells to tumor antigens are enhanced, thus the immune response to tumor is improved [7]. The duration of inflammatory response induced by lipid adjuvant such as MPLA is short and the effective activation time is no more than 24 hours [8]. When different types of antigens (tumor-associated antigens or tumor-specific antigens) are delivered together, the enhancement effect of immune adjuvants will be different. Combining various adjuvants or developing a new more effective adjuvant, which can improve the effectiveness of a single adjuvant in the vaccine while preventing from being suppressed by non-apoptotic tumor cells.
In this review, the research status and application prospects of lipid-based adjuvant in tumor vaccines were briefly discussed. The two applications of adjuvants are elaborated, and the most mature tumor immunostimulant: the function, chemical synthesis, combination strategy and derivatives of lipid A were discussed in detail. In addition, the problems and insights of immune adjuvants in the field of tumor vaccines would be proposed based on the current research.