Recombinant expression, downstream optimization, and therapeutic evaluation of recombinant human interleukin-37 for cancer therapy

Biotechnol Lett. 2024 Dec;46(6):1269-1291. doi: 10.1007/s10529-024-03539-3. Epub 2024 Oct 18.

Abstract

Interleukin-37 is a cytokine with potent immunosuppressive properties that has been shown to have potential to treat autoimmune and chronic inflammatory diseases, as well as certain types of cancer. IL-37 is a 19 kDa protein which interacts with proteins in receptor-dependent and receptor-independent pathways. The expression of the IL-37 protein cloned into the pET-28a vector was optimized in Rosetta 2(DE3) after comparing its expression with Rosetta-gami 2(DE3) and Rosetta 2(DE3) pLysS, which was then used for the large-scale production of IL-37. IMAC purification of IL-37 yielded > 97% pure 0.9 mg/mL protein from auto-induced fermentation. The IC50 value of IL-37 was < 1 µM, which was similar to that of doxorubicin, and proliferation of > 80% of all cancer cells was inhibited by 100 µg/mL of IL-37 protein. IL-37 may be a promising theragnostic target for cancer due to its comparable IC50 value with that of doxorubicin.

Keywords: Cancer therapy; Computational analysis; IMAC purification; Media optimization; Recombinant IL-37; Soluble expression.

MeSH terms

  • Antineoplastic Agents / pharmacology
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cloning, Molecular
  • Doxorubicin / pharmacology
  • Escherichia coli / genetics
  • Gene Expression
  • Humans
  • Interleukin-1* / genetics
  • Interleukin-1* / metabolism
  • Neoplasms* / drug therapy
  • Recombinant Proteins* / genetics
  • Recombinant Proteins* / metabolism
  • Recombinant Proteins* / pharmacology

Substances

  • IL37 protein, human
  • Interleukin-1
  • Recombinant Proteins
  • Antineoplastic Agents
  • Doxorubicin