Abstract P6-10-06: Inducing immune responses to tumor associated carbohydrate antigens by a carbohydrate mimetic peptide vaccine: Clinical experience in phase I and phase II trials
Authors: T Kieber-Emmons, LF Hutchins, PD Emanuel, A Pennisi, E Siegel, F Jousheghany, BM Karbassi, I Makhoul
Journal: Cancer Research (2017)

Abstract Active immunization of cancer patients to induce de novo functional anti-tumor immune responses is an alternative/complementary approach to chemotherapy. Tumor vaccines hold the potential to deliver durable, specific and systemic anti-tumor responses in patients. We have been developing active vaccination strategies targeting tumor associated carbohydrate antigens (TACAs) using carbohydrate mimetic peptides. TACAs play roles in initiation and metastasis of cancer and considered as common targets shared by many tumor types. TACA support cell survival that can be interrupted by anti-carbohydrate antibodies. An early-phase 3+3 clinical trial was conducted to evaluate the feasibility, safety and immune functionality of a carbohydrate mimetic-peptide (CMP) vaccine referred to as P10s, which can induce TACA reactive, proapoptotic antibodies. In this trial a dose-escalation trial of vaccine plus adjuvant was conducted in two cohorts of 3 subjects each. Patients were restricted to females of all races with histologically or cytologically confirmed stage IV breast cancer who had stable disease and a positive recall-antigen response. P10s was synthesized with the Pan-T-cell epitope PADRE and formulated at 300 and 500 µg/injection with MONTANIDE™ ISA 51 VG for the 1st and 2nd cohorts, respectively. Doses of the appropriate formulation of the vaccine were administered to research participants subcutaneously on weeks 1, 2, 3, 7 and 19. Blood samples were collected at various time points and tested for presence and functionality of antibodies. Antibody response to P10s and in particular against the ganglioside GD2 was measured by ELISA. Binding of pre-immune and post-immune sera was assessed against breast cancer cell lines. Vaccination generates IgG response with serum antibodies capable of inhibiting tumor growth in spheroid culture of breast cancer cell lines. The vaccine induced antibodies in all 6 subjects, displaying significant cytotoxic activity against several representative human breast-cancer cell lines. Caspase 3 was involved in the postimmune serum-mediated apoptosis. No cytotoxicity toward a normal breast epithelial cell line was detected. Apoptosis and caspase 3 activation seems to be involved in anti-tumor cell activity. Immunization with the P10s vaccine was found to be safe and tolerable, and induces functional antibodies that potentially have a cell-death-mediated therapeutic benefit. Incubation of spheroids with post-immune serum further sensitized cells to drugs, improving the efficacy of drug treatment at lower doses. The data suggest that the vaccine-induced anti-tumor immune response in combination with standard of care chemotherapy may further improve clinical outcome. Consequently, we are testing the vaccine in a Phase II study in the neoadjuvant setting. 5 Cohorts of 5 patients each administered with the vaccine at different schedules of chemotherapy are being assessed for immune response to the vaccine as in the Phase I study and if the combination approach contributes to a difference in pathological complete response (PCR) from chemotherapy alone. Citation Format: Kieber-Emmons T, Hutchins LF, Emanuel PD, Pennisi A, Siegel E, Jousheghany F, Karbassi BM, Makhoul I. Inducing immune responses to tumor associated carbohydrate antigens by a carbohydrate mimetic peptide vaccine: Clinical experience in phase I and phase II trials [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P6-10-06.