Oncotarget

Clinical Research Papers:

Targeting tumor-associated carbohydrate antigens: a phase I study of a carbohydrate mimetic-peptide vaccine in stage IV breast cancer subjects

Laura F. Hutchins, Issam Makhoul, Peter D. Emanuel, Angela Pennisi, Eric R. Siegel, Fariba Jousheghany, Xueyan Guo, Anastas D. Pashov, Behjatolah Monzavi-Karbassi and Thomas Kieber-Emmons _

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Oncotarget. 2017; 8:99161-99178. https://doi.org/10.18632/oncotarget.21959

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Abstract

Laura F. Hutchins1,6, Issam Makhoul1,6, Peter D. Emanuel1,6, Angela Pennisi1,6, Eric R. Siegel2, Fariba Jousheghany3, Xueyan Guo4, Anastas D. Pashov5, Behjatolah Monzavi-Karbassi3,6 and Thomas Kieber-Emmons3,6

1Departments of Medicine, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA

2Departments of Biostatistics, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA

3Departments of Pathology, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA

4Department of Gastroenterology, Third Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China

5Stephan Angelov Institute of Microbiology, Bulgarian Academy of Sciences, Sofia, Bulgaria

6Winthrop P. Rockefeller Cancer Institute, Little Rock, Arkansas, USA

Correspondence to:

Thomas Kieber-Emmons, email: tke@uams.edu

Keywords: tumor-associated carbohydrate antigens, cancer vaccine, clinical trial, breast cancer, peptide mimotopes

Received: August 23, 2017     Accepted: October 10, 2017     Published: October 23, 2017

ABSTRACT

Tumor-associated carbohydrate antigens (TACAs) support cell survival that could be interrupted by anti-TACA antibodies. Among TACAs that mediate cell survival signals are the neolactoseries antigen Lewis Y (LeY) and the ganglioside GD2. To induce sustained immunity against both LeY and GD2, we developed a carbohydrate mimicking peptide (CMP) as a surrogate pan-immunogen that mimics both. This CMP, referred to as P10s, is the N-terminal half of a peptide vaccine named P10s-PADRE, the C-terminal half of which (PADRE) is a Pan-T-cell epitope. A Phase I dose-escalation trial of P10s-PADRE plus adjuvant MONTANIDE™ ISA 51 VG was conducted in subjects with metastatic breast cancer to test 300 and 500 μg/injection in two cohorts of 3 subjects each. Doses of the P10s-PADRE vaccine were administered to research participants subcutaneously on weeks 1, 2, 3, 7 and 19. Antibody responses to P10s, GD2, and LeY were measured by ELISA. The P10s-PADRE vaccine induced antibodies specifically reactive with P10s, LeY and GD2 in all 6 subjects. Serum antibodies displayed Caspase-3-dependent apoptotic functionality against LeY or GD2 expressing breast cancer cell lines. Immunization with the P10s-PADRE vaccine was well-tolerated and induced functional antibodies, and the data suggest potential clinical benefit.


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