Molecular and Macroscopic Therapeutic Systems for Cytokine‐Based Cancer Immunotherapy

Abstract

Cytokines are proteins that mediate and regulate inflammation and immune responses in the body. While several cytokines have been investigated as antitumor agents in multiple clinical trials due to their potent immunomodulatory activities, the unfavorable pharmacokinetics of recombinant cytokines resulted in substantial side effects and a low therapeutic index. Because these factors have hampered the further development of cytokine-based immunotherapy, bioengineered technologies that can enhance therapeutic efficacy and lower systemic toxicities are in high demand. In this review, the molecular modification of cytokines and delivery system for the spatiotemporal distribution of exogenous cytokines as well as macroscopic delivery systems for endogenous cytokine production based on gene therapy and immunomodulator-mediated therapy will be discussed.

A nanoadjuvant that dynamically coordinates innate immune stimuli activation enhances cancer immunotherapy and reduces immune cell exhaustion

“…To enhance cancer immunotherapy, immune cells that have been weakened or inactivated in cancer patients need to be reinvigorated to respond specifically and dynamically to cancer cells that are alive, mutated and adapted in a complex and dynamic way 1 . Because the activation of resting antigen-presenting cells (APCs) is a crucial step in the initiation of adaptive antitumour immunity, nanotechnology-based material design with a 'pathogen-mimicking' strategy has utilized key features of the size, shape and surface-molecule organization of pathogens to control innate immunity in the context of cancer immunotherapy [2][3][4][5][6][7][8][9][10][11][12][13][14] . However, the maturation of APCs is regulated not only by the nature of the APC maturation stimuli but also by the duration, combination and timing of stimulation, which collectively affect subsequent T-cell responses 6,15,16 .…”

Near-Infrared Triggered Self-Accelerating Nanozyme Camouflaged with a Cancer Cell Membrane for Precise Targeted Imaging and Enhanced Cancer Immunotherapy

“…6−8 The immune response targets and destroys cancer cells based on specific antigen recognition with low side effects. 9 Although immunotherapies, including cytokine therapy, 10 chimeric antigen receptor T-cell therapy, 11 immune checkpoint block (ICB) therapy, 12 and tumor vaccines, 13 have achieved impressive clinical advances for various cancers, the therapeutic efficiency is often modest and severely restricted by the inadequate immunogenicity and immune resistance of cancer cells. 14 Therefore, an ideal alternative for effective antitumor immunity should simultaneously satisfy the adequate release of damage-associated molecular patterns (DAMPs) and the inhibition of immune resistance, which must be urgently addressed.…”

“…Immunotherapy has emerged as a promising therapeutic approach for cancer treatment by harnessing the inherent immune system of patients. – Compared to traditional surgical resection, radiotherapy, and chemotherapy, immunotherapy has the advantages of eliminating primary tumors as well as treating advanced metastasis and recurrence. – The immune response targets and destroys cancer cells based on specific antigen recognition with low side effects . Although immunotherapies, including cytokine therapy, chimeric antigen receptor T-cell therapy, immune checkpoint block (ICB) therapy, and tumor vaccines, have achieved impressive clinical advances for various cancers, the therapeutic efficiency is often modest and severely restricted by the inadequate immunogenicity and immune resistance of cancer cells . Therefore, an ideal alternative for effective antitumor immunity should simultaneously satisfy the adequate release of damage-associated molecular patterns (DAMPs) and the inhibition of immune resistance, which must be urgently addressed.…”