We have developed a peptide mimotope-based cancer vaccine, P10s-PADRE, targeting tumor associated carbohydrate antigens (TACAs). We have previously shown safety, feasibility and induction of immune response in a phase I clinical trial in stage IV breast cancer patients. In the current clinical trial, immunization with P10s-PADRE vaccine is combined with the standard-of-care chemotherapy in neo-adjuvant setting in subjects diagnosed with early stage ER-positive breast cancer. Various schedules (timing of vaccination doses relative to chemo) for combination therapy were tested. Immunological endpoint variable include antibody response and activation of natural killer (NK) cells as tested in peripheral blood mononuclear cells. Tumor size before treatment and after surgery was measured for each subject. The secondary endpoint was pathologic complete response (pCR). We observed induction of antibody response and activation of NK cells independent of each other. Vaccination affected the expression of several NK markers including CD94 and NKp46 as we observed a significant upregulation of NKp46 (median = 1.79, P<0.0001), and CD94 (median = 1.50, P<0.0001) in response to immunization. The data indicate a significant increase in serum IFN-γ (Median=1.74, P=0.0016) upon vaccination. Increase in IFN-γ was positively correlated with increase in both CD69 (r = 0.46, P=0.0321) and NKp46 (r = 0.39, P=0.0763) on CD56-dim NK cells. Tumor shrinkage was associated with an increase in NK cells, upregulation of NKp46 and CD94 molecules, and increase in frequency of NKp46-positive and CD94-positive CD56-dim NK cells. Among 25 subjects enrolled in 5 different immunization schedules, 5 experienced complete eradication of their primary tumors that was associated with vaccine induced increase in the frequency of CD94-positive CD56-dim NK cells (p= 0.0473). The results are intriguing and warrant expansion of the immunologically effective combination schedule to further establish the clinical efficacy along with potential biomarkers of response.

Citation Format: Issam Makhoul, Fariba Jousheghany, Saddam Mohammed, Eric Siegel, Angela Pennisi, J Thaddeus Beck, Laura Hutchins, Thomas Kieber-Emmons, Behjatolah Monzavi-Karbassi. Immunization of breast cancer patients in combination with standard-of-care chemotherapy: Results of a phase Ib clinical trial [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P3-09-18.