Engineered Medicines to Mitigate Resistance to Cancer Immunotherapy

About this Research Topic

Background

Cancer immunotherapy leverages the potential of tumor-specific cytotoxic T lymphocytes (CTLs) to elicit an antitumor immune response and prolongs survival of patients with rapidly fatal cancers. Among the different types of cancer immunotherapy, immune checkpoint blockades (ICBs) and chimeric antigen receptor T-cell (CAR-T) based therapies have had the broadest impact in treating number of different malignancies. Recent advances in the development and application of antibodies targeting checkpoint blockades cytotoxic T lymphocyte antigen 4 (CTLA4) or the programmed cell death 1 (PD1)–PD1 ligand 1 (PD-​L1) axis have been approved for use in the treatment of different cancers. Similarly, genetically engineered T cells expressing chimeric antigen receptor (CAR) specifically binds to cancer cell surface antigens and has significantly contributed to provide therapeutic benefit for numerous cancers.

Despite the great potential of cancer immunotherapy, there are tremendous challenges in clinical application due to the limited response rates driven by the intrinsic and adaptive immune resistance. The efficacy of drugs has been limited, due to nonspecific distribution, side effects and short circulation time, offering an evolutionary opportunity for nanomedicine to circumvent these drawbacks and improve therapeutic efficacy. Many cancers have evolved various mechanisms to evade immunological surveillance, such as the inhibitory immune checkpoint of the CD47-SIRPα signaling pathway. By targeting this signaling pathway, researchers have developed diverse nanovehicles with different loaded drugs and modifications in anticancer treatment

Accordingly, this Research Topic aims to address the following themes cancer immunotherapy resistances:

1. How intrinsic and adaptive immune resistance is manifested in different scenarios in cancers.

2. Strategies for overcoming resistance with engineered medicines.

3. Approaches involving monotherapy (monoclonal antibodies), combinatorial therapy (codelivery of disparate drugs with varied pharmacokinetic profiles), and nanomedicine-based cancer immunotherapy.

4. Engineering stimuli-responsive nanotherapeutics (micelle, lipid, and supramolecular nanoparticles) using the characteristics of the tumor microenvironment to curb the immune resistance.

5. Clinical translation of engineered medicine-based immunotherapy to overcome the therapeutic hindrance due to tumor heterogeneity, diverse immune phenotypes, complex tumor microenvironment, and the translational gap between experimental mice and human patients

Keywords: Cancer Immunotherapy, Engineered Medicines, Immunotherapy, Targeted Therapy

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