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Immunoselection of Breast and Ovarian Cancer Cells with Trastuzumab and Natural Killer Cells: Selective Escape of CD44high/CD24low/HER2low Breast Cancer Stem Cells
Cancer Research, 10/21/09

Reim F et al. – The observation that the "relapsed" in vitro cultures show practically identical HER2 surface expression and susceptibility toward ADCC suggests that the administration of trastuzumab beyond relapse might be considered, especially when combined with an immune–stimulatory treatment that targets the escape variants.

Exclusive Author Commentary
Jörg Wischhusen, 12/07/09

As it happens, this project had initially aimed at something completely different, i.e. the exploration of mechanisms that may render breast cancer cells refractory to ADCC effected by trastuzumab and natural killer cells. However, the generation of immunoresistant sublines failed completely. Instead, we observed the selective survival of a small subpopulation of cancer stem cell (CSC)-like breast cancer cells with low HER2 expression which then regenerated a phenocopy of the original culture - safe for an enrichment in CSC. Assuming that our model system approximates the in vivo interactions between tumor, antibody and NK cells reasonably well, these findings bear some clinical implications: The bad news is that cancer stem cells may not be eliminated by trastuzumab and NK cells. The good news is that most of the surviving cells do not remain in their protected CSC-like state but differentiate and thus become susceptible again to the treatment. Accordingly, a rechallenge with trastuzumab may still be effective after relapse. But I might also be over-interpreting these data...

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