Proof-of-concept study to enumerate large oncosomes using the RareCyte CTC platform

Liquid biopsy attention goes to circulating tumor cells and cell-free DNA; this AACR 2024 proof-of-concept poster from CellCarta asks whether large oncosomes — cell-free, CK/EpCAM-positive objects larger than 4 µm — can be counted from the same metastatic breast cancer specimens already drawn for CTC analysis on the RareCyte platform.

Presented by CellCarta.

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  • Large oncosomes could be counted from specimens already collected for CTC analysis, and they outnumbered the CTCs. Objects that were CK/EpCAM positive, nucleus free, CD45 negative and larger than 4 µm with evidence of a membrane at 40X were scored as large oncosomes across 15 patient specimens; LO counts ran higher than CTC counts (Wilcoxon signed rank p=6.10E-5) and the two correlated strongly (Spearman r=0.91, p=8.11E-5).
  • HER2 was read on the oncosomes themselves, at a rate that tracked the HER2-positive CTCs. HER2-positive large oncosomes appeared in 8 of 9 (89%) blood smears against a mean fluorescence intensity cutoff of 350, and the proportion of HER2-overexpressing oncosomes correlated with the proportion of HER2-positive CTCs (Spearman r=0.71, p=0.05), a comparison the authors note may be affected by low CTC counts.
  • The plasma left over after CTC analysis still supported ERBB2 copy number testing. cfDNA extracted from that plasma was of suitable quality for dPCR, and ERBB2 amplification status was correctly identified for 6 of 7 (85%) patients with available tumor copy number data, though concentrations varied and the lowest reading came from the one sample whose ERBB2 result disagreed.

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