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. 2016 Apr 22;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

Roisin E O'Cearbhaill  1   2 , Govind Ragupathi  3 , Jianglong Zhu  4 , Qian Wan  5 , Svetlana Mironov  6 , Guangbin Yang  7 , Maria K Spassova  8 , Alexia Iasonos  9 , Sara Kravetz  10 , Ouathek Ouerfelli  11 , David R Spriggs  12   13 , Samuel J Danishefsky  14 , Paul J Sabbatini  15   16
Affiliations

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

Roisin E O'Cearbhaill et al. Cancers (Basel). .

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.

Keywords: QS-21; immunogenicity; ovarian cancer; peptide vaccine; remission; unimolecular vaccine.

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Figures

Figure 1
Figure 1
Unimolecular pentavalent vaccine.
Figure 2
Figure 2
Anti-sTn (IgG and IgM) antibody titers of patients vaccinated with the unimolecular pentavalent-KLH vaccine.
Figure 3
Figure 3
Progression-free survival in months for patients enrolled on the study (n = 24, four patients are censored).
See this image and copyright information in PMC

References

    1. Markman M., Markman J., Webster K., Zanotti K., Kulp B., Peterson G., Belinson J. Duration of response to second-line, platinum-based chemotherapy for ovarian cancer: Implications for patient management and clinical trial design. J. Clin. Oncol. 2004;22:3120–3125. doi: 10.1200/JCO.2004.05.195. - DOI - PubMed
    1. Syrios J., Banerjee S., Kaye S.B. Advanced epithelial ovarian cancer: From standard chemotherapy to promising molecular pathway targets—where are we now? Anticancer Res. 2014;34:2069–2077. - PubMed
    1. Sabbatini P., Spriggs D.R. Consolidation for ovarian cancer in remission. J. Clin. Oncol. 2006;24:537–539. doi: 10.1200/JCO.2005.04.5138. - DOI - PubMed
    1. Zhang S., Zhang H.S., Cordon-Cardo C., Ragupathi G., Livingston P.O. Selection of tumor antigens as targets for immune attack using immunohistochemistry: Protein antigens. Clin. Cancer Res. 1998;4:2669–2676. - PubMed
    1. Ragupathi G., Liu N.X., Musselli C., Powell S., Lloyd K., Livingston P.O. Antibodies against tumor cell glycolipids and proteins, but not mucins, mediate complement-dependent cytotoxicity. J. Immunol. 2005;174:5706–5712. doi: 10.4049/jimmunol.174.9.5706. - DOI - PubMed