TY - GEN
T1 - 546 A phase I dose escalation study of STEMVAC, a multi-antigen, multi-epitope Th1 selective plasmid-based vaccine, targeting stem cell associated proteins in patients with advanced breast cancer
AU - Disis, Mary
AU - Stanton, Sasha
AU - comments, See all authors in
PY - 2022/11/8
Y1 - 2022/11/8
N2 - Background Cancer stem cell or epithelial/mesenchymal transition antigens could have utility in vaccines for cancer treatment and prevention. We identified class II binding T-cell epitopes from non-mutated tumor antigens that selectively elicit a Th1 response. We constructed a 5 antigen (CD105-Yb-1-SOX2-CDH3-MDM2) multi-epitope plasmid-based vaccine; STEMVAC, and conducted a Phase I dose escalation study in patients with advanced breast cancer. Methods Patients with advanced HER2 negative breast cancer previously treated and in remission were sequentially enrolled to 3 dose arms: 150, 300, or 600mcg of STEMVAC. Vaccines were given monthly intradermally for three doses with rhu-GM-CSF (100mcg) as adjuvant. Two booster immunizations (same dose) were given 3 and 6 months after the third vaccine. Primary endpoints were safety and immunogenicity. Secondary endpoints included persistence of the immune response after vaccination and assessment of potential stimulation of T-regulatory (Treg) cells or myeloid derived suppressor cells (MDSC) to the overexpressed non-mutated antigens expressed in STEMVAC. Antigen specific immunity was measured by IFN-gamma (g) and IL-10 ELISPOT. Immune cells were evaluated by flow cytometry. Results Seventy-five percent of patients were hormone receptor positive and 25% triple negative (TNBC). Patient characteristics, including breast cancer subtype, did not vary significantly between doses (all p>0.1). The vast majority of adverse events (AE), 98%, were grades 1/2. The most common AE were injection site reactions, flu-like syndrome, and transient leukopenia and lymphopenia. Arm 1 (150mcg) generated transient low levels of IFN-g secreting T-cells to a median of 1 antigen per patient and considered the least immunogenic dose. Arm 2 (300mcg) resulted in a mean response (sum of all antigens) of 1 antigen specific T-cell per 2500 (1:2500) PBMC at week 16 (p
AB - Background Cancer stem cell or epithelial/mesenchymal transition antigens could have utility in vaccines for cancer treatment and prevention. We identified class II binding T-cell epitopes from non-mutated tumor antigens that selectively elicit a Th1 response. We constructed a 5 antigen (CD105-Yb-1-SOX2-CDH3-MDM2) multi-epitope plasmid-based vaccine; STEMVAC, and conducted a Phase I dose escalation study in patients with advanced breast cancer. Methods Patients with advanced HER2 negative breast cancer previously treated and in remission were sequentially enrolled to 3 dose arms: 150, 300, or 600mcg of STEMVAC. Vaccines were given monthly intradermally for three doses with rhu-GM-CSF (100mcg) as adjuvant. Two booster immunizations (same dose) were given 3 and 6 months after the third vaccine. Primary endpoints were safety and immunogenicity. Secondary endpoints included persistence of the immune response after vaccination and assessment of potential stimulation of T-regulatory (Treg) cells or myeloid derived suppressor cells (MDSC) to the overexpressed non-mutated antigens expressed in STEMVAC. Antigen specific immunity was measured by IFN-gamma (g) and IL-10 ELISPOT. Immune cells were evaluated by flow cytometry. Results Seventy-five percent of patients were hormone receptor positive and 25% triple negative (TNBC). Patient characteristics, including breast cancer subtype, did not vary significantly between doses (all p>0.1). The vast majority of adverse events (AE), 98%, were grades 1/2. The most common AE were injection site reactions, flu-like syndrome, and transient leukopenia and lymphopenia. Arm 1 (150mcg) generated transient low levels of IFN-g secreting T-cells to a median of 1 antigen per patient and considered the least immunogenic dose. Arm 2 (300mcg) resulted in a mean response (sum of all antigens) of 1 antigen specific T-cell per 2500 (1:2500) PBMC at week 16 (p
M3 - Other contribution
T3 - Articles, Abstracts, and Reports
ER -