Epidermal growth factor receptor-targeted immunomagnetic liposomes for circulating tumor cell enumeration in non-small cell lung cancer treated with epidermal growth factor receptor-tyrosine kinase inhibitors

Abstract Objectives To establish a circulating tumor cell (CTC) enrichment system for non-small cell lung cancer (NSCLC) patients who received first-line treatment with epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (EGFR-TKI), using EGFR magnetic liposomes (EGFR-ML). Materials and methods An inverted evaporation method was used to develop antibody modified EGFR-ML. Peripheral blood was collected from NSCLC patients who underwent first-line EGFR-TKI treatment for CTC enumeration. Results Protein electrophoresis, magnetic saturation curve, and ultraviolet absorption spectrum showed successful incorporation of the EGFR antibody on the surface of the magnetic microspheres, and the development of EGFR-ML was ascertained based on cell morphology and particle size. Using EGFR-ML, CTC were successfully enriched from blood samples and were identified in 77.3% (99/128) of the cohort. When compared to the 21L858R variant, EGFR-19del showed lower CTC counts by EGFR-ML (CTC EGFR ). At one month after EGFR-TKI, a lower CTC EGFR was associated with partial response (PR) during treatment (CTC EGFR P  = 0.027). In addition, patients with a lower CTC EGFR at 3 months after EGFR-TKI achieved a longer progression-free survival (PFS) [CTC EGFR P  = 0.042]. CTC EGFR significantly increased at the time of RECIST-progressive disease (RECIST-PD). Representative cases showed that CTC EGFR might increase before and beyond RECIST-PD until no clinical benefit could be acquired from EGFR-TKI. Conclusion We showed that establishing a CTC enrichment system by antibody modified EGFR-ML in NSCLC is feasible. CTC enumeration by EGFR-ML may have the potential to supplement RECIST in dynamically monitoring the response of NSCLC patients’ to first-line EGFR-TKI.