Frontiers in Immunology (Apr 2022)

Recent Advances in IL-13Rα2-Directed Cancer Immunotherapy

  • Karin M. Knudson,
  • SuJin Hwang,
  • Mondona S. McCann,
  • Bharat H. Joshi,
  • Syed R. Husain,
  • Raj K. Puri

DOI
https://doi.org/10.3389/fimmu.2022.878365
Journal volume & issue
Vol. 13

Abstract

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Interleukin-13 receptor subunit alpha-2 (IL-13Rα2, CD213A), a high-affinity membrane receptor of the anti-inflammatory Th2 cytokine IL-13, is overexpressed in a variety of solid tumors and is correlated with poor prognosis in glioblastoma, colorectal cancer, adrenocortical carcinoma, pancreatic cancer, and breast cancer. While initially hypothesized as a decoy receptor for IL-13-mediated signaling, recent evidence demonstrates IL-13 can signal through IL-13Rα2 in human cells. In addition, expression of IL-13Rα2 and IL-13Rα2-mediated signaling has been shown to promote tumor proliferation, cell survival, tumor progression, invasion, and metastasis. Given its differential expression in tumor versus normal tissue, IL-13Rα2 is an attractive immunotherapy target, as both a targetable receptor and an immunogenic antigen. Multiple promising strategies, including immunotoxins, cancer vaccines, and chimeric antigen receptor (CAR) T cells, have been developed to target IL-13Rα2. In this mini-review, we discuss recent developments surrounding IL-13Rα2-targeted therapies in pre-clinical and clinical study, including potential strategies to improve IL-13Rα2-directed cancer treatment efficacy.

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