Engineering New Approaches to Cancer Vaccines

Abstract

Recently, a number of promising approaches have been developed using synthetic chemistry, materials science, and bioengineering-based strategies to address challenges in the design of more effective cancer vaccines. At the stage of initial priming, potency can be improved by maximizing vaccine delivery to lymph nodes. Because lymphatic uptake from peripheral tissues is strongly size-dependent, antigens and adjuvants packaged into optimally-sized nanoparticles access the lymph node with much greater efficiency than unformulated vaccines. Once primed, T cells must home to the tumor site. Because T cells acquire the necessary surface receptors in the local lymph node draining the tissue of interest, vaccines must be engineered that reach organs such as the lung and gut, which are common sites of tumor lesions but inaccessible by traditional vaccination routes. Particulate vaccine-carriers can improve antigen exposure in these organs, resulting in greater lymphocyte priming. Immunomodulatory agents can also be injected directly into the tumor site to stimulate a systemic response capable of clearing even distal lesions; materials have been designed that entrap or slowly release immunomodulators at the tumor site, reducing systemic exposure and improving therapeutic efficacy. Finally, lessons learned from the design of biomaterial-based scaffolds in regenerative medicine have led to the development of implantable vaccines that recruit and activate antigen presenting cells to drive anti-tumor immunity. Overall, these engineering strategies represent an expanding toolkit to create safe and effective cancer vaccines.

Beyond the tumour microenvironment

“…Additionally, different approaches have been considered to maximise vaccine delivery to the draining lymph nodes, one component of the TOE, with the goal of enhancing the priming of tumour‐specific T lymphocytes, and thus antitumoural immunity. Such strategies include the packaging of antigens and/or adjuvants into bioengineered nanoparticles . A final point to be considered here concerning the distant action of the immune system from a therapeutic point of view is the fact that current cancer immunotherapies often have significant adverse systemic effects, which could potentially be alleviated therapeutically via the targeting of elements located beyond the TME.…”

A primer on recent developments in cancer immunotherapy, with a focus on neoantigen vaccines

“…Further afield, cancer vaccine engineering has emerged to offer benefits such as lymph node targeting, reduced systemic toxicity, elimination of ex vivo expansion requirements, and controlled release of immunomodulators while ignoring suppressive signals [94][95][96] .…”

Enhancing vaccine effectiveness with delivery technology

“…The range of natural TLR ligand adjuvants associated with bacterial vectors also offers a way of ensuring or biasing a more comprehensive response [37]*. Such a combination of responses has been shown effective for infectious disease (H1N1 influenza) and additional cancer treatments [38–40]. To this stage, however, few delivery vectors have been designed or utilized to direct a combination of Th1/Th2 responses.…”