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

Stefania Cuzzubbo, Sara Mangsbo, Divya Nagarajan, Kinana Habra, Alan Graham Pockley, Stephanie E B McArdle

Journal: Frontiers in immunology 2021;11():615240

PMID: 33679703

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.

Copyright © 2021 Cuzzubbo, Mangsbo, Nagarajan, Habra, Pockley and McArdle.

Address: Université de Paris, PARCC, INSERM U970, 75015, Paris, France.; Laboratoire de Recherches Biochirurgicales (Fondation Carpentier), Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Européen Georges Pompidou, Paris, France.; Ultimovacs AB, Uppsala, Sweden.; Department of Pharmaceutical Biosciences, Science for Life Laboratory, Uppsala University, Uppsala, Sweden.; Department of Immunology, Genetics and Clinical pathology Rudbeck laboratories, Uppsala University, Uppsala, Sweden.; The School of Science and Technology, Nottingham Trent University, Nottingham, United Kingdom.; The John van Geest Cancer Research Centre, School of Science and Technology, Nottingham Trent University, Nottingham, United Kingdom.; Centre for Health, Ageing and Understanding Disease (CHAUD), School of Science and Technology, Nottingham Trent University, Nottingham, United Kingdom.
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