Photoimmunotherapy of HER2-expressing Breast Cancer Cells

Abstract: Background/Aim: Breast cancer (BC) is the most common malignant disease worldwide. Localized stages of BC can be successfully treated by surgery. However, local recurrence occurs in about 4-10% of patients, requiring systemic treatments that impair the patients’ quality of life and shortens life expectancy. Therefore, new therapeutic options are needed, which can be used intraoperatively and contribute to the complete removal of residual tumor cells in the surgical area. In the present study, we describe a cysteine-modified variant of the anti-HER2 antibody trastuzumab, that was coupled to the silicon phthalocyanine photosensitizer dye WB692-CB1 for the photoimmunotherapy (PIT) of BC. Materials and Methods: The cysteine modified trastuzumab variant was cloned and expressed in Expi293F cells. After purification via immobilized affinity chromatography, the antibody was coupled to the dye. Cell binding of the antibody and the antibody dye conjugate was measured by flow cytometry. After incubation of BC cells with the conjugate and activation of the dye by irradiation with red light, cell viability was determined. Results: The antibody and the conjugate showed specific binding to HER2-expressing BC cells. Treatment of the HER2high BC cell line SK-BR-3 with the conjugate followed by irradiation with a red light dose of 32 J/cm2 led to complete cell killing within 24 h. Conclusion: Our novel antibody dye conjugate represents a promising candidate for intraoperative treatment of localized BC, aiming to eliminate residual tumor cells in the surgical area and potentially reduce local recurrence, thereby improving recovery prospects for BC patients

Location
Deutsche Nationalbibliothek Frankfurt am Main
Extent
Online-Ressource
Language
Englisch
Notes
Cancer genomics & proteomics. - 21, 4 (2024) , 361-367, ISSN: 1109-6535

Event
Veröffentlichung
(where)
Freiburg
(who)
Universität
(when)
2024

DOI
10.21873/cgp.20453
URN
urn:nbn:de:bsz:25-freidok-2535712
Rights
Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
Last update
25.03.2025, 1:47 PM CET

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Time of origin

  • 2024

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