Immunologic Analysis of a Phase I/II Study of Vaccination with MAGE-3 Protein Combined with the AS02B Adjuvant in Patients with MAGE-3-Positive Tumors

Abstract

In a phase I/II study, patients with solid metastatic MAGE-3-positive tumors, mainly melanoma, were vaccinated with recombinant MAGE-3 protein combined with the immunologic adjuvant AS02B comprised of MPL and QS21 in an oil-in-water emulsion. The recombinant MAGE-3 protein was made up of a partial sequence of the protein D (ProtD) antigen of Haemophilus influenzae fused to the MAGE-3 sequence. The vaccine was given intramuscularly at 3-week intervals. Patients whose tumors stabilized or regressed after 4 vaccinations received 2 additional vaccinations at 6-week intervals. MAGE-3 and ProtD antibody and cellular immune responses were monitored after vaccination. Ninety-six percent (23/24) of the patients vaccinated with MAGE-3 protein in AS02B adjuvant elicited a significant anti-MAGE-3 IgG antibody response after 4 vaccinations, and all developed anti-ProtD IgG antibodies. For the detection of T-cell activity, total peripheral blood mononuclear cells were restimulated in vitro with MAGE-3- or ProtD-loaded autologous mature dendritic cells. In 30% of the evaluable patients vaccinated with the adjuvanted recombinant protein, IFNgamma production was increased in response to MAGE-3, and 2 patients (14% of evaluable patients) had a concomitant increase in IL-5 production. In 37% and 43% of the patients, respectively, IFNgamma or IL-5 production was increased in response to ProtD. It is concluded that vaccination of advanced cancer patients with MAGE-3 self-antigen in AS02B adjuvant is able to elicit MAGE-3-specific antibody and a T-cell response.

Booster vaccination of cancer patients with MAGE-A3 protein reveals long-term immunological memory or tolerance depending on priming

“…We have also reported that absence of adjuvant in the vaccine during priming resulted in the failure of the vaccine to induce detectable antibody and T cell responses, an observation confirmed by others (42,43). Our study now demonstrates that immune memory was also persistent in patients primed with MAGE-A3 protein without an inflammatory adjuvant.…”

Oxidation of Ovarian Epithelial Cancer Cells by Hypochlorous Acid Enhances Immunogenicity and Stimulates T Cells that Recognize Autologous Primary Tumor

“…Dendritic cell maturation was induced by using either CD40 agonistic antibodies (mouse IgG1, clone mAb89, Immunotech), or a lipopolysaccharide A analogue (31,32), monophosphoryl lipid A (MPL: detoxified lipid A derived from Salmonella; Avanti Polar Lipids, Inc.), chosen because both reagents have previously been approved for use in clinical trials (31 -35). Dendritic cells were cocultured with oxidized SK-OV-3 and then treated with CD40 antibody (100-1,000 ng/mL) or MPL (50-200 ng/mL) for 24 h at 37jC/5%CO 2 AIM-V CM.…”

Nonclinical reproductive and developmental safety evaluation of the MAGE-A3 Cancer Immunotherapeutic, a therapeutic vaccine for cancer treatment

“…One dose of the MAGE-A3 Cancer Immunotherapeutic consisted of 300 g recombinant MAGE-A3 antigen (ProteinD-MAGE-A3-His; recMAGE-A3) [41] and a fixed dose of the AS15 immunostimulant, containing MPL (GSK Vaccines, Rixensart, Belgium), QS-21 (Antigenics Inc, a wholly owned subsidiary of Agenus Inc., Lexington, MA, USA), CpG 7909 synthetic oligodeoxynucleotides containing unmethylated CpG motifs, and liposome (50 g MPL, 50 g QS-21 and 420 g CpG 7909). The control was a 0.9% sterile sodium chloride solution (saline).…”