Photoimmunotherapy: A New Method for Targeting EGFR in Bladder Cancer - Expert Commentary

Clinically-localized bladder cancer is amenable to local treatments because of its accessibility. A team of investigators led by Dr. Piyush Agarwal at the National Institutes of Health developed a novel way to target bladder cancers that express epidermal growth factor receptor (EGFR). By combining infrared radiation with an anti-EGFR antibody panitumumab labeled with the photo-absorber, IR dye 700Dx.

The investigators found that while bladder cancers express the EFGR in varying degrees, squamous cell carcinomas (SCC) have the highest expression levels of this target. This led them to focus their efforts in studying this approach to the SCC cell line UMUC-5. Because EGFR is localized to the basal layer of normal urothelium but is present in both the luminal and basal layers of urothelial cells in bladder cancer, it offers a selective advantage for targeting the cancer cells while sparing the normal urothelium.

The investigators show that In vitro, the antibody-photo absorber conjugate demonstrated effectiveness in causing cell death in UMUC-5 cells. In vivo, UMUC-5 xenograft tumors treated with the panitumumab- photo absorber conjugate and infrared light grew slower than xenografts that were treated with conjugate but not infrared light.

This novel approach offers better selectivity and molecularly-targeted phototherapy for bladder cancer. Identification of additional targets and synthesis of antibodies to target the common urothelial carcinoma histologic subtype of bladder cancer, promises to broadly extend the utility of this therapeutic modality. Clinical trials that translate this concept to the bedside are needed.

Written By: Bishoy Faltas MD

Read the Abstract

Railkar R, Krane LS, Li QQ, Sanford T, Siddiqui MR, Haines D, Vourganti S, Brancato SJ, Choyke PL, Kobayashi H, Agarwal PK. Epidermal Growth Factor Receptor (EGFR) Targeted Photoimmunotherapy (PIT) for the Treatment of EGFR expressing Bladder Cancer. Mol Cancer Ther. 2017 Jun 15. pii: molcanther.0924.2016. doi: 10.1158/1535-7163.MCT-16-0924
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