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.

From synthesis to biologics: preclinical data on a chemistry derived anticancer vaccine.

A fully synthetic anticancer vaccine 2 has been prepared via bioconjugation of unimolecular pentavalent construct 1-containing five prostate and breast cancer associated carbohydrate antigens, Globo-H, GM2, STn, TF and Tn-to maleimide-modified carrier protein KLH. An improved conjugation protocol has been developed, which allowed us to obtain a higher epitope ratio of the unimolecular pentavalent glycopeptide antigen to the carrier protein (505/1 versus 228/1 for the previous version). KLH conjugate 2 has been subsequently submitted to preclinical immunogenic evaluation in mice in the presence of QS-21 as an adjuvant.

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

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.

Preparation and evaluation of unimolecular pentavalent and hexavalent antigenic constructs targeting prostate and breast cancer: a synthetic route to anticancer vaccine candidates.

Several novel, fully synthetic, carbohydrate-based antitumor vaccines have been assembled. Each construct consists of multiple cancer-related antigens displayed on a single polypeptide backbone. Recent advances in synthetic methodology have allowed for the incorporation of a complex oligosaccharide terminating in a sialic acid residue (i.

Synthesis of selected LeY and KH-1 analogues: a medicinal chemistry approach to vaccine optimization.

[structure: see text] As part of our ongoing anticancer vaccine program, we recently found that antibodies generated in response to the KH-1-KLH construct recognized not only KH-1 antigen but also the Lewis Y (Le(y)) antigen as well, with antibody titer levels much higher than those observed after immunization with individual Le(y)-KLH vaccine constructs. In an attempt to explore the structure-antigenic relationship of these carbohydrate epitopes, several analogues of both KH-1 and Le(y) were synthesized. A convergent synthetic approach to the analogues was designed on the basis of well-established glycal methodology, employing a minimum number of building blocks to generate competent antigens with high stereoselectivity and reasonable yield.