A pilot study incorporating HER2-directed dendritic cells into neoadjuvant therapy of early stage HER2+ER- breast cancer
Hatem Soliman, Amy L. Aldrich, Neveen Abdo, Hyo S. Han, Aixa Soyano, Ricardo Costa, Avan Armaghani, John V. Kiluk, Nazanin Khakpour, Marie Catherine Lee, Susan Hoover, Christine Laronga, Bethany L. Niell, Blaise Mooney, R. Jared Weinfurtner, Marilin Rosa, Brian J. Czerniecki
Abstract
Type 1 dendritic cell vaccines targeting HER2 (HER2-DC1) reinvigorates antitumor immunity which correlates with neoadjuvant therapy response. A pilot trial (clinicaltrials.gov,NCT03387553,1/2/2018) using HER2-DC1 pre-neoadjuvant therapy evaluated feasibility/safety and pathologic response rates/immunogenicity. Stage II-III ER-HER2+ breast cancer patients prescribed neoadjuvant docetaxel/carboplatin/trastuzumab/pertuzumab (TCHP) were enrolled. HER2-DC1 (2×10 7 cells/vaccine) was given for 3 weeks prior to chemotherapy intranodal (IN) 1x/week (Arm A), IN 2x/week (Arm B), and 2x/week alternating intratumoral (IT) and IN (Arm C). HER2 ELISPOT counts (EHC) and immunofluorescence analysis of biopsies were performed. Six patients enrolled in Arms A and B, 18 patients in Arm C. Neoadjuvant HER2-DC1 demonstrated no unexpected safety signals. Pathologic complete response rates (pCR) across arms A, B, C were 42.8%, 66.6%, and 72.7%. Intranodal HER2-DC1 increased EHC, but IT + IN HER2-DC1 reduced EHC, possibly due to increased T cell tumor trafficking. Immunofluorescence showed increased T cell infiltration following IT + IN injections. Additional IT HER2-DC1 investigation is warranted.