Cancer Vaccines: Adjuvant Potency, Importance of Age, Lifestyle, and Treatments

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.

Cancer Vaccines: Promising Therapeutics or an Unattainable Dream

“…Many cancer vaccines are poorly immunogenic and lack clinical efficacy. To trigger more durable immune responses, adjuvants are commonly incorporated into cancer vaccine formulations to increase the efficacy of the vaccine in numerous ways, including stabilization of the antigen in the circulation, increasing the association between the antigen and APCs, and promote cytokine production which all culminate in activation of anti-cancer immune cells [ 168 , 169 ]. Adjuvants can be broadly characterized into 2 categories; (i) ‘Depot’ adjuvants, which are those that prolong antigen availability (e.g., mineral salts such as aluminum hydroxide, emulsions and liposomes).…”

“…Other examples of depot adjuvants are mineral salts such as alum, which is however rarely used for cancer vaccines as it only triggers a Th2-mediated immune response and not a Th1 type response, which is more beneficial to eradicate tumors [ 172 ]. (ii) Immunostimulatory adjuvants including Toll Like receptor agonists, saponins, STINGS and cytokines which function as potentiators of innate and adaptive immune responses (reviewed in detail in [ 168 ]). The most extensively characterized and widely used immunostimulatory adjuvant is the cytokine GM-CSF which has been incorporated into multiple cancer vaccines including the Provenge and GVAX [ 173 , 174 ].…”

Stay on Target: Reengaging Cancer Vaccines in Combination Immunotherapy

“…The most commonly used adjuvant cytokines are GM-CSF and IL-2. However, numerous additional cytokines, including IFN⍺, IFN γ , IL-12, IL-15, IL-18 and IL-21, have demonstrated efficacy as vaccine adjuvants [ 48 ].…”

Immunotherapy and Vaccination in Surgically Resectable Non-Small Cell Lung Cancer (NSCLC)

“…Whereas ICIs boost inactivated responses of effector T cells, vaccination can potentially activate naive T cells with tumor specificity and in this way broaden the tumor-specific immune responses. Therefore, combining cancer vaccines, which can elicit specific T cell responses, with ICIs represent attractive therapeutic options [ 123 , 124 ].…”