Bioengineering and Immunotherapy – a future synergy

The stimulation of the immune system is, for long, recognized as an effective strategy to fight cancer, since the first observations of this topic in the XIX century and the work of William B. Coley. However, the true potential of immunotherapy was only revealed in the last decade, with immune checkpoint inhibitors (2018 Nobel Prize in Medicine and Physiology) and CAR-T cells arriving to the oncological clinical practice. An additional immunotherapy approach, strongly tested in the last 20 years, refers to dendritic cell (DC) -based vaccines for anti-tumour therapy. These cells act as sentinels of our own immune system, having a key role in triggering and modulating anti-tumour immune responses. Despite several hundreds of clinical trials, showing a clear safety profile of these vaccines, clinical outputs have been somehow inconsistent. With a clear, globally recognized potential and with an increasing knowledge of some of the limitations of these vaccines, several novel strategies have been studies and tested. In this review, researchers from the University of Coimbra, the portuguese pharmaceutical company Tecnimede Group and University of Aveiro, collected, studied and structured all the current data on one of the most promising strategies to boost DC-based vaccines efficacy: the use of biomaterials in the form of scaffolds, implantable or injected, programmed to act as platforms to modulate endogenous DCs, releasing tumour antigens and DC activation and maturation agents. In this publication, the authors also discuss on how nextgeneration cancer therapies, such as neoantigens and immune checkpoint inhibitors, can be used as combination therapies with the novel biomaterial vaccines.

Authors and Affiliations:

João Calmeiro^a,b, Mylene Carrascal^b, Célia Gomes^c,d, Amílcar Falcão^a,e, Maria Teresa Cruzab, and Bruno Miguel Neves^f

^a Faculty of Pharmacy, University of Coimbra, 3000-548, Coimbra – Portugal

^b Center for Neuroscience and Cell Biology, University of Coimbra, 3004 -504 Coimbra - Portugal

^c Coimbra Institute for Clinical and Biomedical Research, Faculty of Medicine, University of Coimbra, Coimbra - Portugal

^d Center for Innovation in Biomedicine and Biotechnology, University of Coimbra, Coimbra –Portugal

^e Coimbra Institute for Biomedical Imaging and Translational Research (CIBIT), University of Coimbra, Coimbra -Portugal

^f Department of Medical Sciences and Institute of Biomedicine – iBiMED, University of Aveiro, 3810-193, Aveiro – Portugal

Abstract:

Dendritic cells (DCs) are central players in the immune system, with an exquisite capacity to initiate and modulate immune responses. These functional characteristics have led to intense research on the development of DC-based immunotherapies, particularly for oncologic diseases. During recent decades, DC-based vaccines have generated very promising results in animal studies, and more than 300 clinical assays have demonstrated the safety profile of this approach. However, clinical data are inconsistent, and clear evidence of meaningful efficacy is still lacking. One of the reasons for this lack of evidence is the limited functional abilities of the used ex vivo-differentiated DCs. Therefore, alternative approaches for targeting and modulating endogenous DC subpopulations have emerged as an attractive concept. Here, we sought to revise the evolution of several strategies for the in situ mobilization and modulation of DCs. The first approaches using chemokine-secreting irradiated tumor cells are addressed, and special attention is given to the cutting-edge injectable bioengineered platforms, programmed to release chemoattractants, tumor antigens and DC maturating agents. Finally, we discuss how our increasing knowledge of DC biology, the use of neoantigens and their combination with immune checkpoint inhibitors can leverage the refinement of these polymeric vaccines to boost their antitumor efficacy.

Journal: Journal for ImmunoTherapy of Cancer, from Springer Nature

Link: https://jitc.biomedcentral.com/articles/10.1186/s40425-019-0716-8