Engineering interferons and interleukins for cancer immunotherapy

• Published in: Advanced drug delivery reviews Vol. 182; p. 114112
• Main Authors: Holder, Patrick G., Lim, Shion A., Huang, Christine S., Sharma, Preeti, Dagdas, Yavuz S., Bulutoglu, Beyza, Sockolosky, Jonathan T.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01-03-2022
• Subjects: Bioengineering - methods; Biomimetics; Cell therapy; Cytokine engineering; Cytokines; Drug delivery; Drug Delivery Systems - methods; Genetic Engineering - methods; Humans; Hydrogen-Ion Concentration; Immune signaling; Interferons - adverse effects; Interferons - metabolism; Interferons - pharmacokinetics; Interferons - pharmacology; Interleukins - adverse effects; Interleukins - metabolism; Interleukins - pharmacokinetics; Interleukins - pharmacology; Ligand-receptor interaction; Neoplasms - drug therapy; Neoplasms - pathology; Protein engineering; CLL; CDC; MDSC; EpCAM; RAS; GVHD; IL-23; TNF; TSCM; IL-21; CDR; CAIX; PI3K; GM-CSF; TFH; PD-1 or CD279; PFS; Cytokine engineering; CEA; IFNγ; IFNα; NSG; DARPin; BCG; IFNλ; IL-4; IL-15; IL-2; IL-12; IL-6; IL-7; i.v; SEC; IFNLR; RCC; Teff; IL-18; IL-21R or CD360; IL-2v; HGFβ; KD; IFNGR; KE; MSC; Protein engineering; CD; cDC1; Cmax; sdAb; BMT; ICB; AKT; γc or CD132; IL-2R; ECM; ICI; mAb; CTLA-4 or CD152; PAMP; STAT; scFv; TAA; IL-2Rβγ or CD122/CD132; TIL; MTD; TIR; ADA; DC; PD-L1 or CD274; ILC; EDB; IL-12Rβ1; Cell therapy; EDA; IL-12Rβ2; CTCL; Ligand-receptor interaction; ISGs; AICD; HSA; IL-18Rα; HSC; IL-2Rα or CD25; IL-18Rβ; LSC; Th17; TMDD; AML; Cytokines; CAF; s.c; TYK2; MAPK; G-CSF; MMP; CAR; HLA; FcγR; NK; IND; TCM; IL-2Rβ or CD122; TCR; tdLN; CRS; IgG; Drug delivery; ORR; ADCP; EGFR; AEs; NHL; FcRn; S1PR1; c-Met; ADCC; Fc; Fab; Treg; IFNAR; PBMCs; TME; HPV16; Immune signaling; PSMA; PEG; APC; GD2; PD; IL-7Rα or CD127; Jak; PDGF; IL-18BP; TGFβ; IL-15Rα or CD215; PK; TEM; DAMP
• ISSN: 0169-409X; 1872-8294
• DOI: 10.1016/j.addr.2022.114112

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•Cytokines play key roles in the regulation of innate and adaptive antitumor immunity but have poor drug-like properties.•Advances in cytokine biology, protein engineering, and immunotherapy have reinvigorated interest in cytokine therapeutics.•Engineered cytokines with tailored functions show promising preclinical results and have given rise to clinical candidates.•Genetic engineering is enabling installation of enhanced cytokines as part of next-generation cellular therapies.
Cytokines are a class of potent immunoregulatory proteins that are secreted in response to various stimuli and act locally to regulate many aspects of human physiology and disease. Cytokines play important roles in cancer initiation, progression, and elimination, and thus, there is a long clinical history associated with the use of recombinant cytokines to treat cancer. However, the use of cytokines as therapeutics has been limited by cytokine pleiotropy, complex biology, poor drug-like properties, and severe dose-limiting toxicities. Nevertheless, cytokines are crucial mediators of innate and adaptive antitumor immunity and have the potential to enhance immunotherapeutic approaches to treat cancer. Development of immune checkpoint inhibitors and combination immunotherapies has reinvigorated interest in cytokines as therapeutics, and a variety of engineering approaches are emerging to improve the safety and effectiveness of cytokine immunotherapy. In this review we highlight recent advances in cytokine biology and engineering for cancer immunotherapy.