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.
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.
Gynecologic Medical Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA. gynbreast@mskcc.org.|Department of Medicine, Weill Cornell Medical College, New York, NY 10065, USA. gynbreast@mskcc.org.
Roisin E
RE
O'Cearbhaill
Melanoma & Immunotherapeutics Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA. ragupatg@mskcc.org.
Govind
G
Ragupathi
Chemical Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA. Jianglong.Zhu@utoledo.edu.
Jianglong
J
Zhu
Chemical Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA. wanqian@hust.edu.cn.
Qian
Q
Wan
Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA. radlana22@gmail.com.
Svetlana
S
Mironov
Chemical Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA. yangg4@mskcc.org.
Guangbin
G
Yang
Chemical Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA. mspassova1@gmail.com.
Maria K
MK
Spassova
Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA. iasonosa@mskcc.org.
Alexia
A
Iasonos
Gynecologic Medical Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA. KravetzS@mskcc.org.
Sara
S
Kravetz
Chemical Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA. o-ouerfelli@ski.mskcc.org.
Ouathek
O
Ouerfelli
Gynecologic Medical Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA. spriggsd@mskcc.org.|Department of Medicine, Weill Cornell Medical College, New York, NY 10065, USA. spriggsd@mskcc.org.
David R
DR
Spriggs
Chemical Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA. s-danishefsky@ski.mskcc.org.
Samuel J
SJ
Danishefsky
Gynecologic Medical Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA. sabbatip@mskcc.org.|Department of Medicine, Weill Cornell Medical College, New York, NY 10065, USA. sabbatip@mskcc.org.
Paul J
PJ
Sabbatini
QS-21; immunogenicity; ovarian cancer; peptide vaccine; remission; unimolecular vaccine