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Cancers 2016, 8(4), 46; doi:10.3390/cancers8040046

A Phase I Study of Unimolecular Pentavalent (Globo-H-GM2-sTn-TF-Tn) Immunization of Patients with Epithelial Ovarian, Fallopian Tube, or Peritoneal Cancer in First Remission

1
Gynecologic Medical Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
2
Department of Medicine, Weill Cornell Medical College, New York, NY 10065, USA
3
Melanoma & Immunotherapeutics Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
4
Chemical Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
5
Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
6
Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
Current Address: Department of Chemistry & Biochemistry, The University of Toledo, Toledo, OH 43606, USA
Current Address: Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, School of Pharmacy, Huazhong University of Science and Technology, Wuhan 430030, Hubei, China
*
Author to whom correspondence should be addressed.
Academic Editor: Vita Golubovskaya
Received: 8 March 2016 / Revised: 12 April 2016 / Accepted: 13 April 2016 / Published: 22 April 2016
(This article belongs to the Special Issue Cancer Immunotherapies)
View Full-Text   |   Download PDF [1397 KB, uploaded 22 April 2016]   |  

Abstract

We conducted a phase I study in ovarian cancer patients to evaluate the safety and immunogenicity of a synthetic unimolecular pentavalent carbohydrate vaccine (Globo-H, GM2, sTn, TF, and Tn) supported on a peptide backbone, conjugated to keyhole limpet haemocyanin (KLH), and mixed with immunological adjuvant QS-21. Twenty-four advanced-stage, poor-risk, first-remission ovarian cancer patients were enrolled from January 2011–Septermber 2013. Three dose levels were planned (25, 50, 100 mcg) with three cohorts of six patients each, with an additional 6-patient expansion cohort at the MTD. ELISA serologic IgM and IgG responses for each antigen was defined as positive response if antibody titers were ≥1:80 over the respective patient’s pre-vaccination serum. The study would be considered positive if at least four of 12 patients treated at the MTD showed immune responses for at least three of the five antigens. Twenty-four patients (median age, 54 years [range, 36–68]) were included in the safety analysis. Histology was high-grade serous in 22 patients (92%); 18 had stage III and six stage IV disease. The vaccine was well-tolerated at all doses, with no DLTs. At the highest treated dose, IgG and/or IgM responses were recorded against ≥3 antigens in 9/12 patients (75%), ≥4 in 7/12 (58%), and 5 in 3/12 (25%). With a median follow-up of 19 months (range, 2–39), 20 patients (83%) recurred and six (25%) died. The unimolecular pentavalent vaccine construct was shown to be safe and immunogenic. Such a construct greatly simplifies regulatory requirements and manufacturing, facilitates scalability, and provides adaptability. View Full-Text
Keywords: peptide vaccine; unimolecular vaccine; QS-21; ovarian cancer; remission; immunogenicity peptide vaccine; unimolecular vaccine; QS-21; ovarian cancer; remission; immunogenicity
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

O’Cearbhaill, R.E.; Ragupathi, G.; Zhu, J.; Wan, Q.; Mironov, S.; Yang, G.; Spassova, M.K.; Iasonos, A.; Kravetz, S.; Ouerfelli, O.; Spriggs, D.R.; Danishefsky, S.J.; Sabbatini, P.J. A Phase I Study of Unimolecular Pentavalent (Globo-H-GM2-sTn-TF-Tn) Immunization of Patients with Epithelial Ovarian, Fallopian Tube, or Peritoneal Cancer in First Remission. Cancers 2016, 8, 46.

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