Modes of Action of TLR7 Agonists in Cancer Therapy

Abstract

From the numerous Toll-like receptor agonists, only TLR7 agonists have been approved for cancer treatment, although they are current restricted to topical application. The main target cells of TLR7 agonists are plasmacytoid dendritic cells, producing IFN-α and thus acting on other immune cells. Thereby dendritic cells acquire enhanced costimulatory and antigen-presenting capacity, priming an adaptive immune response. Besides NK cells, antigen-specific T cells are the main terminal effectors of TLR7 agonists in tumor therapy. This qualifies TLR7 agonists as vaccine adjuvants, which is currently being tested in clinical trials. However, the systemic application of TLR7 agonists shows insufficient efficacy, most likely owing to toxicity-limited dosing. The use of TLR7 agonists in combinational therapy holds the promise of synergistic activity and lower required doses.

Keywords::

• cancer immunotherapy
• imiquimod
• innate immunity
• TLR7

Financial & competing interests disclosure

S Kobold and S Endres are supported by the Munich biotech cluster m⁴, by a grant from 4SC (Munich), by the melanoma research alliance (grant number N269626), by the Graduiertenkolleg 1202 ‘Oligonucleotides in cell biology and therapy’ funded by the Deutsche Forschungsgemeinschaft and by the training network ‘i-Target’ funded by the elite network of Bavaria. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Additional information

Funding

S Kobold and S Endres are supported by the Munich biotech cluster m⁴, by a grant from 4SC (Munich), by the melanoma research alliance (grant number N269626), by the Graduiertenkolleg 1202 ‘Oligonucleotides in cell biology and therapy’ funded by the Deutsche Forschungsgemeinschaft and by the training network ‘i-Target’ funded by the elite network of Bavaria. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.