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Antibody-dye Conjugates Targeting EGFR and HER2 for the Photoimmunotherapy of Bladder Cancer
Fabian Huber1,2, Isis Wolf1,2,3, Jonas Storz4
1Department of Urology, Medical Center-University of Freiburg, Freiburg, Germany.
Background/Aim:
Although there are curative treatment options for non-muscle-invasive bladder cancer, the recurrence of this tumor is high. Therefore, novel targeted therapies are needed for the complete removal of bladder cancer cells in stages of localized disease, in order to avoid local recurrence, to spare bladder cancer patients from stressful and expensive treatment procedures and to increase their quality of life and life expectancy. This study tested a new approach for the photoimmunotherapy (PIT) of bladder cancer.
Materials And Methods:
We generated a cysteine modified recombinant version of the antibody cetuximab targeting the epidermal growth factor receptor (EGFR) on the surface of bladder cancer cells. Then, we coupled the novel photoactivatable phthalocyanine dye WB692-CB1 via a maleimide linker to the free cysteines of the antibody. PIT was performed by incubating bladder cancer cells with the antibody dye conjugate followed by irradiation with visible red light.
Results:
The conjugate was able to induce specific cytotoxicity in EGFR-positive bladder cancer cells in a light dose-dependent manner. Enhanced cytotoxicity in RT112 bladder cancer cells was evoked by addition of a second antibody dye conjugate targeting HER2 or by repeated cycles of PIT.
Conclusion:
Our new antibody dye conjugate targeting EGFR-expressing bladder cancer cells is a promising candidate for the future PIT of bladder cancer patients.
Insights
This study developed a new photoimmunotherapy (PIT) using an antibody-dye conjugate to target EGFR-expressing bladder cancer cells. The novel approach shows promise for effectively eliminating localized bladder tumors and improving patient outcomes.
Area of Science:
- Oncology
- Immunotherapy
- Biotechnology
Background:
- Non-muscle-invasive bladder cancer has a high recurrence rate despite existing treatments.
- Novel targeted therapies are crucial to improve patient quality of life and life expectancy.
- Current treatments for bladder cancer can be stressful and costly.
Purpose of the Study:
- To test a new photoimmunotherapy (PIT) approach for bladder cancer.
- To develop a targeted therapy for complete removal of localized bladder cancer cells.
- To reduce local recurrence rates and improve patient outcomes.
Main Methods:
- Generated a cysteine-modified cetuximab antibody targeting epidermal growth factor receptor (EGFR).
- Coupled the antibody with a photoactivatable phthalocyanine dye (WB692-CB1) via a maleimide linker.
- Performed PIT by incubating bladder cancer cells with the conjugate and irradiating with red light.
Main Results:
- The antibody-dye conjugate induced specific cytotoxicity in EGFR-positive bladder cancer cells.
- Cytotoxicity was dependent on the light dose.
- Enhanced cell killing was observed with a second antibody targeting HER2 or with repeated PIT cycles.
Conclusions:
- A novel antibody-dye conjugate targeting EGFR-expressing bladder cancer cells shows potential for PIT.
- This approach may offer a promising future therapy for bladder cancer patients.
- Further research could lead to improved treatment strategies and patient quality of life.
