Abstract
Although the discovery and characterization of multiple tumor antigens have sparked the development of many antigen/derived cancer vaccines, many are poorly immunogenic and thus, lack clinical efficacy. Adjuvants are therefore incorporated into vaccine formulations to trigger strong and long-lasting immune responses. Adjuvants have generally been classified into two categories: those that ‘depot’ antigens (e.g. mineral salts such as aluminum hydroxide, emulsions, liposomes) and those that act as immunostimulants (Toll Like Receptor agonists, saponins, cytokines). In addition, several novel technologies using vector-based delivery of antigens have been used. Unfortunately, the immune system declines with age, a phenomenon known as immunosenescence, and this is characterized by functional changes in both innate and adaptive cellular immunity systems as well as in lymph node architecture. While many of the immune functions decline over time, others paradoxically increase. Indeed, aging is known to be associated with a low level of chronic inflammation—inflamm-aging. Given that the median age of cancer diagnosis is 66 years and that immunotherapeutic interventions such as cancer vaccines are currently given in combination with or after other forms of treatments which themselves have immune-modulating potential such as surgery, chemotherapy and radiotherapy, the choice of adjuvants requires careful consideration in order to achieve the maximum immune response in a compromised environment. In addition, more clinical trials need to be performed to carefully assess how less conventional form of immune adjuvants, such as exercise, diet and psychological care which have all be shown to influence immune responses can be incorporated to improve the efficacy of cancer vaccines. In this review, adjuvants will be discussed with respect to the above-mentioned important elements.
Highlights
Therapeutic cancer vaccines represent an attractive strategy to stimulate protective anti-tumor immunity in combination with standard therapies
The developed tumor microenvironment is typically immunosuppressive and is characterized by the presence of exhausted T and NK cells and the accumulation of several suppressive immune cells, such as T regulatory cells, T helper type-2 (Th2) CD4+ T cells, tumor-associated macrophages (TAMs), and myeloid-derived suppressor cells (MDSCs) [50,51,52,53], in addition to which the activation state of T cells will be regulated by co-inhibitory pathways
Multiple cancer vaccines have not yet achieved significant clinical efficacy. Their limited efficacy is certainly in part related to the poor immunogenicity of the vaccine itself in many cases, and to the difficulty of inducing an effective immune response in the compromised immune system of cancer patients
Summary
Therapeutic cancer vaccines represent an attractive strategy to stimulate protective anti-tumor immunity in combination with standard therapies. Clinical responses have been rather anecdotal [48, 49] The reasons for those failed trials are not fully understood but are most likely related to the stage of the disease treated, an inherent difficulty to mount a strong cellular immune response to non-live vaccine entities when older and the choice of antigens, adjuvant and the suppressive nature of the tumor microenvironment. Among these reasons, the difficulty of achieving strong cellular immune responses is likely a major factor to consider.
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