Research Topic

Development and Potential Mechanisms of Low Molecular Weight Drugs for Cancer Immunotherapy

About this Research Topic

Low molecular weight therapeutics, including proteins, peptides, small molecules, aptamers, proteolysis targeting chimera (PROTAC), and repurposed drugs, have gained great progress with their advantages over antibodies, such as greater tumor penetration, oral bioavailability, easy modification and fine ...

Low molecular weight therapeutics, including proteins, peptides, small molecules, aptamers, proteolysis targeting chimera (PROTAC), and repurposed drugs, have gained great progress with their advantages over antibodies, such as greater tumor penetration, oral bioavailability, easy modification and fine control of bioavailability. However, their application and regulatory role in cancer immunotherapy remain to be investigated in depth.

There are three major aspects to regulate cancer immunity: activation of innate immune response, modulation of the immunosuppressive cell subsets, and immune checkpoints blockade. In activating innate immune response (especially dendritic cells), small molecule agonists targeting Toll-like receptors (TLRs) or cGAS-STING for immunotherapy have achieved good results in clinical trials, but their side effects are great concerns when administrated systemically. Manipulating the function of immunosuppressive cells (such as tumor-associated macrophages (TAMs) and regulatory T cells) could be effective to create a favorable tumor microenvironment. But the failure of the phase III clinical trial of Epacadostat (IDO1 inhibitor, TAM polarization agent) has pushed us to explore more else where. Low molecular weight therapeutics targeting the immune checkpoints through unleashing the inhibition of T cells have recently attracted increasing attention. BMS-986189 (a PD-1/PD-L1 blocking macrocyclic peptide), CA-170 (a small molecule), ALX148 (a protein blocking CD47/SIRPα) and IMP321 (a protein blocking LAG-3/HLA-DR) are all undergoing clinical trials.

In addition, some FDA approved drugs (such as Metformin and Aspirin) have been reported to play an important role to regulate cancer immunity. But novel low molecular weight therapeutics such as aptamers and PROTAC drugs still remain to be extensively investigated. Also, the underlying regulatory mechanisms of these agents on different cell subsets in the tumor microenvironment are largely unknown.

The aim of this Research Topic is to discuss the current progress on low molecular weight therapeutics and the underlying mechanisms for cancer immunotherapy. We welcome submissions of Original Research and Review articles on the following sub-topics:

• Discovery and development of low molecular weight drugs targeting immune checkpoints, TLRs, STING and other therapeutic agents for cancer immunotherapy. Such as proteins, peptides, small molecules, aptamers, PROTAC, and drug repurposing.
• The potential regulation mechanisms of low molecular weight drugs on immune cells and stromal cells in the tumor microenvironment.


Keywords: Cancer immunotherapy, Drug discovery, Low molecular weight drug, Immune checkpoint, Tumor microenvironment


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Submission Deadlines

22 May 2021 Manuscript

Participating Journals

Manuscripts can be submitted to this Research Topic via the following journals:

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Topic Editors

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Submission Deadlines

22 May 2021 Manuscript

Participating Journals

Manuscripts can be submitted to this Research Topic via the following journals:

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