Abstract P2-11-12: Novel protocol combining metronomic nant-paclitaxel with HER2-targeted natural killer cells (innate immunotherapy) for HER2-positive metastatic breast cancer

Background. Natural killer (NK) cells are an important effector cell type for adoptive cancer immunotherapy. Phase 1 clinical trials in patients with advanced cancers demonstrated the safety of unmodified, activated NK-92 cells (aNK), with no evidence of cytokine storm from 18 infusions delivered over 6 months; clinical responses were observed in a subset of patients. Like T cells, NK cells can be engineered to express chimeric antigen receptors (CARs) to enhance their antitumor activity. A stable clonal HER2-specific NK-92 cell line (HER2.taNK) mediated selective and sequential killing of HER2-expressing MDA-MB-453 cells in vitro (Schönfeld. MolTher. 2015;23:330-338). In addition, HER2.taNK cells were enriched in MDA-MB-453/EGFP xenografts and reduced the number of pulmonary metastasis in a renal cell carcinoma model, suggesting that HER2.taNK cells are a promising clinical candidate for use in adoptive cancer immunotherapy. Metronomic (low-dose, continuous) chemotherapy can be more effective than high-dose therapy in patients with advanced breast cancer (Montagna. Canc. Treat. Rev. 2014;40:922-950). Here we evaluate HER2.taNK cells in combination with metronomic nant-paclitaxel (lyophilized polymeric micellar formulation of paclitaxel) in a mouse model of HER2-positive breast cancer to determine the feasibility of a human clinical trial of HER2.taNK in combination with metronomic nant-paclitaxel.Methods. HER2.taNK cells were generated as described previously (Schönfeld. M...
Source: Cancer Research - Category: Cancer & Oncology Authors: Tags: Poster Session Abstracts Source Type: research