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.