Abstract
Two decades of clinical cancer research with dendritic cell (DC)-based vaccination have proved that this type of personalized medicine is safe and has the capacity to improve survival, but monotherapy is unlikely to cure the cancer. Designed to empower the patient’s antitumor immunity, huge research efforts are set to improve the efficacy of next-generation DC vaccines and to find synergistic combinations with existing cancer therapies. Immune checkpoint approaches, aiming to breach immune suppression and evasion to reinforce antitumor immunity, have been a revelation in the immunotherapy field. Early success of therapeutic antibodies blocking the programmed death-1 (PD-1) pathway has sparked the development of novel inhibitors and combination therapies. Hence, merging immunoregulatory tumor-specific DC strategies with PD-1-targeted approaches is a promising path to explore. In this review, we focus on the role of PD-1-signaling in DC-mediated antitumor immunity. In the quest of exploiting the full potential of DC therapy, different strategies to leverage DC immunopotency by impeding PD-1-mediated immune regulation are discussed, including the most advanced research on targeted therapeutic antibodies, lessons learned from chemotherapy-induced immune activation, and more recent developments with soluble molecules and gene-silencing techniques. An overview of DC/PD-1 immunotherapy combinations that are currently under preclinical and clinical investigation substantiates the clinical potential of such combination strategies.
Highlights
Dendritic cells (DCs) are key antigen-presenting cells capable of presenting tumor antigens to T lymphocytes [1] and promoting innate immunity via, e.g., natural killer (NK) cells [2] and γδ T cells [3]
Targeting programmed death-1 (PD-1) in DC Therapy antigen-specific and immunoregulatory qualities, DCs can be furnished with tumor antigens and other targeted molecules via different techniques [7,8,9]
Since its second-place ranking as a potential target for immunotherapy at the Immunotherapy Agent Workshop of the National Cancer Institute in 2007 research on the inhibitory checkpoint programmed death-1 (PD-1)/programmed death ligand (PDL) pathway has boosted massively
Summary
Dendritic cells (DCs) are key antigen-presenting cells capable of presenting tumor antigens to T lymphocytes [1] and promoting innate immunity via, e.g., natural killer (NK) cells [2] and γδ T cells [3]. As an alternative to human(ized) mABs, different blocking moieties with advanced target specificity and affinity and reduced toxicity profiles are under investigation, including chimeric fusion proteins (AMP224, extracellular domain of PD-L2, and an Fc portion of IgG) and nanotechnologies [nanoparticles [122] and nanobodies ((123), Theravectys, Ablynx)] Research in this area is limited, these alternative blockers have interesting features because of their size, stability, and pharmacodynamical properties [124], which might pave the way for implementation in combination therapy with DCs. Comparable to the systemic antibody approach is the use of sPD-1 receptor, which only contains the extracellular domain of the PD-1 molecule and can ligate to PD-Ls, making them inaccessible for interaction with PD-1 molecules on immune effector cells. Therapy cycles of cyclophosphamide, TCRtransduced PBMC, anti-PD-1 therapy, DC vaccination, and rhIL-2
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
