Abstract
Treatment options for triple-negative breast cancer (TNBC) remain limited, and the highly heterogeneous nature of these tumors often contributes to therapeutic resistance. While we have previously demonstrated that antibodies targeting multiple distinct mutated cell surface proteins (MSPs) unique to a given tumor can disrupt tumor growth in mice, the feasibility of this approach in TNBC remains uncertain. Here, we used the murine EMT6 cell line to model TNBC and produced polyclonal antibodies (pAbs) targeting 12 different EMT6-specific MSPs. Of these, 9 bound to EMT6 cells in a cumulative manner without detectable non-tumor binding. Administering a cocktail of these 9 MSP-targeting pAbs to EMT6 tumor-bearing mice in combination with anti-PD-1 delayed tumor growth and improved survival. Analyses of TNBC patients in The Cancer Genome Atlas revealed that the tumors of a larger proportion of these patients harbored > 10 MSPs as compared to individuals with other breast cancer types (69% vs. 42%). Together, these results highlight the promise of using antibodies directed against MSPs expressed by TNBC tumor cells to kill tumor cells in vivo, providing a unique approach to individualized cancer patient care with the potential to achieve superior patient outcomes through the elimination of heterogeneous tumor cell populations.
Data availability
The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.
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SP contributed to the conceptualization, data curation, data analysis, investigation, methodology, project administration, and writing/review/editing of the manuscript. GS contributed to the conceptualization, data curation, formal analysis, investigation, methodology and preparation/review of manuscript. YS, MA, CH, RB, LM, FZ, and MF contributed to data curation, investigation, methodology and review of the manuscript. DK contributed to the conceptualization, data analysis, investigation, project administration, and writing/review/editing of the manuscript.
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Informed consent was obtained from all individual participants included in the study following the University Vermont Institutional Review Board Regulations (Study #00000317). All animal work was completed in accordance with University of Vermont Institutional Animal Care and Use Committee (Protocol #18 − 002). All animal work was performed in accordance with the ARRIVE guidelines. This study was performed in accordance with the ethical standards as defined in the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards.
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Pero, S.C., Shukla, G.S., Sun, Y. et al. Novel antibody cocktail therapy targeting extracellular tumor-specific mutations to treat EMT6 cell line-derived triple-negative breast cancer. Sci Rep (2026). https://doi.org/10.1038/s41598-026-46751-z
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DOI: https://doi.org/10.1038/s41598-026-46751-z
