Immunization of metastatic breast cancer patients with a fully synthetic globo H conjugate: A phase I trial

Abstract

The carbohydrate antigen globo H commonly found on breast cancer cells is a potential target for vaccine therapy. The objectives of this trial were to determine the toxicity and immunogenicity of three synthetic globo H-keyhole limpet hemocyanin conjugates plus the immunologic adjuvant QS-21. Twenty-seven metastatic breast cancer patients received five vaccinations each. The vaccine was well tolerated, and no definite differences were observed among the three formulations. Serologic analyses demonstrated the generation of IgM antibody titers in most patients, with minimal IgG antibody stimulation. There was significant binding of IgM antibodies to MCF-7 tumor cells in 16 patients, whereas IgG antibody reactivity was observed in a few patients. There was evidence of complement-dependent cytotoxicity in several patients. Affinity column purification supported the specificity of IgM antibodies for globo H. On the basis of these data, globo H will constitute one component of a polyvalent vaccine for evaluation in high-risk breast cancer patients.

Carbohydrate-based vaccines with a glycolipid adjuvant for breast cancer

“…This vaccine is currently in phase 3 clinical trials, and the GH epitope is manufactured by the programmable one-pot method (26). Although GH-specific IgM was generated in most patients, the level of IgG was low, and patients often reported inflammatory response at the injection site with occasional systemic complaints such as fever, arthralgias, and myalgias (18). All these undesirable symptoms are similar to the reported side effects of QS21 (27)(28)(29).…”

“…GH is also expressed weakly in normal tissue but only restricted to apical epithelial cells at lumen borders, a site that seems to be immune-inaccessible (9,(15)(16)(17). Moreover, higher levels of anti-GH Ab were detected in the plasma of breast cancer patients (18)(19)(20). Our previous study also revealed that the expression of some glycans, such as GH and Stage-specific embryonic antigen 3 (SSEA3) (also called Gb5), was observed on breast cancer cells and breast cancer stem cells (BCSCs) (21).…”

“…A multivalent glycan vaccine or carbohydrate conjugated with a carrier protein and administered with an immunological adjuvant has been adopted to increase the immunogenicity of carbohydrates. As an example, a GH vaccine with ∼700 GH units conjugated to one keyhole limpet hemocyanin (KLH) protein was prepared and administered together with a mixture of saponins called QS21 adjuvant (18,(22)(23)(24)(25), and it had been shown that treatment of mice with GH-KLH/QS21 could induce antisera against GH-positive cell lines without autoimmune reactions (14,23). Furthermore, the vaccine was fairly well-tolerated in a phase I clinical trial for metastatic breast cancer patients.…”

Risk Factors of Breast Cancer among Women in Eastern India: A Tertiary Hospital Based Case Control Study

“…Among the larger studies, the relative risk estimates appeared to decrease by approximately 0.09 for each additional birth (Weir et al, 2007) . Cohort life-table studies of white Catholic nuns have demonstrated the greater mortality due to cancers of the breast and lower mortality due to cancer of the uterine cervix (Gilewski, 1998). Case control studies have indicated pregnancies to be more numerous among controls than among breast cancer patients (Gajalakshmi and Shanta, 1991;Gajalakshmi et al, 1998;2009;Rao, 1994).…”

Carbohydrate microarray for profiling the antibodies interacting with Globo H tumor antigen

“…Furthermore, it has been established that the serum of breast cancer patients contains high levels of antibodies against the Globo H epitope, and this epitope is also targeted by the monoclonal antibodies MBr1 (5-7) and VK-9 (8). As a result, this hexasaccharide has been the focus of studies aimed at anticancer vaccine development (9)(10)(11)(12)(13)(14)(15). Many elegant syntheses of Globo H have been reported (11,(16)(17)(18)(19)(20)(21)(22)(23)(24), including one approach that uses the one-pot programmable oligosaccharide synthesis developed in our laboratory (25).…”