Synapse - Pilot study of a heptavalent vaccine-keyhole limpet hemocyanin conjugate plus QS21 in patients with epithelial ovarian, fallopian tube, or peritoneal cancer

Pilot study of a heptavalent vaccine-keyhole limpet hemocyanin conjugate plus QS21 in patients with epithelial ovarian, fallopian tube, or peritoneal cancer Journal Article

Authors:	Sabbatini, P. J.; Ragupathi, G.; Hood, C.; Aghajanian, C. A.; Juretzka, M.; Iasonos, A.; Hensley, M. L.; Spassova, M. K.; Ouerfelli, O.; Spriggs, D. R.; Tew, W. P.; Konner, J.; Clausen, H.; Abu Rustum, N.; Danishefsky, S. J.; Livingston, P. O.
Article Title:	Pilot study of a heptavalent vaccine-keyhole limpet hemocyanin conjugate plus QS21 in patients with epithelial ovarian, fallopian tube, or peritoneal cancer
Abstract:	Purpose: To characterize the safety and immunogenicity of a heptavalent antigen-keyhole limpet hemocyanin (KLH) plus QS21 vaccine construct in patients with epithelial ovarian, fallopian tube, or peritoneal cancer in second or greater complete clinical remission. Experimental Design: Eleven patients in this pilot trial received a heptavalent vaccine s.c. containing GM2 (10 μg), Globo-H (10 μg), Lewis Y (10 μg), Tn(c) (3 μg), STn(c) (3 μg), TF(c) (3 μg), and Tn-MUC1 (3 μg) individually conjugated to KLH and mixed with adjuvant QS21 (100 μg). Vaccinations were administered at weeks 1, 2, 3, 7, and 15. Periodic blood and urine samples were obtained to monitor safety (complete blood count, comprehensive panel, amylase, thyroid-stimulating hormone, and urinalysis) and antibody production (ELISA, fluorescence-activated cell sorting, and complement-dependent cytotoxicity). Results: Eleven patients were included in the safety analysis; 9 of 11 patients remained on study for at least 2 weeks past fourth vaccination and were included in the immunologic analysis (two withdrew, disease progression). The vaccine was well tolerated. Self-limited and mild fatigue (maximum grade 2 in two patients), fever, myalgia, and localized injection site reactions were most frequent. No clinically relevant hematologic abnormalities were noted. No clinical or laboratory evidence of autoimmunity was seen. Serologic responses by ELISA were largely IgM against each antigen with the exception of Tn-MUC1 where both IgM and IgG responses were induced. Antibody responses were generally undetectable before immunization. After immunization, median IgM titers were as follows: Tn-MUC1, 1:640 (IgG 1:80); Tn, 1:160; TF, 1:640; Globo-H, 1:40; and STn, 1:80. Only one response was seen against Lewis Y; two were against GM2. Eight of nine patients developed responses against at least three antigens. Antibody titers peaked at weeks 4 to 8 in all patients. Fluorescence-activated cell sorting and complement-dependent cytotoxicity analysis showed substantially increased reactivity against MCF7 cells in seven of nine patients, with some increase seen in all patients. Conclusions: This heptavalent-KLH conjugate plus QS21 vaccine safely induced antibody responses against five of seven antigens. Investigation in an adequately powered efficacy trial is warranted. ©2007 American Association for Cancer Research.
Keywords:	adult; clinical article; controlled study; treatment response; aged; middle aged; unclassified drug; human cell; clinical trial; drug tolerability; cancer growth; drug safety; unspecified side effect; outcome assessment; neoplasm staging; ovarian neoplasms; controlled clinical trial; ovary cancer; peritoneum cancer; peritoneal neoplasms; patient monitoring; enzyme linked immunosorbent assay; cancer regression; statistical analysis; cancer vaccine; drug therapy, combination; blood sampling; pilot study; laboratory test; immunogenicity; antibody response; cancer immunization; models, molecular; safety; blood cell count; fallopian tube neoplasms; urinalysis; adjuvants, immunologic; uterus cancer; serology; treatment withdrawal; antibody production; amylase; antibody titer; thyrotropin; complement dependent cytotoxicity; hemocyanin; saponins; vaccines, conjugate; uterine tube; neoplasms, glandular and epithelial; qs 21; fluorescence activated cell sorter; ganglioside gm2 keyhole limpet hemocyanin conjugate; globo h antigen keyhole limpet hemocyanin conjugate; lewis y antigen keyhole limpet hemocyanin conjugate; sialosyl tn antigen keyhole limpet hemocyanin conjugate; thomsen friedenreich antigen keyhole limpet hemocyanin conjugate; tn antigen keyhole limpet hemocyanin conjugate; tn mucin 1 antigen keyhole limpet hemocyanin conjugate
Journal Title:	Clinical Cancer Research
Volume:	13
Issue:	14
ISSN:	1078-0432
Publisher:	American Association for Cancer Research
Date Published:	2007-07-15
Start Page:	4170
End Page:	4177
Language:	English
DOI:	10.1158/1078-0432.ccr-06-2949
PUBMED:	17634545
PROVIDER:	scopus
DOI/URL:	http://www.scopus.com/inward/record.url?eid=2-s2.0-34547127136&partnerID=40&md5=f09dc111bda8fc7a57fdc1914568901d
Notes:	--- - "Cited By (since 1996): 35" - "Export Date: 17 November 2011" - "CODEN: CCREF" - "Source: Scopus"