Year-end Sale % OFF 
Abstract
MAGE-A4 antigen is a cancer-testis antigen that is frequently expressed in tumor tissues. Cholesteryl pullulan (CHP) is a novel antigen delivery system for cancer vaccines. This study evaluated the safety, immune responses and clinical outcomes of patients who received a CHP-MAGE-A4 vaccine. Twenty-two patients with advanced or metastatic cancer were enrolled, and were subcutaneously vaccinated with either 100 μg or 300 μg of CHP-MAGE-A4. Seven and 15 patients, respectively, were repeatedly vaccinated with 100 μg or 300 μg of CHP-MAGE-A4; patients in both groups received a median of 7 doses. No serious adverse events related to the vaccine were observed. Of 7 patients receiving the 100 μg dose, 2 (29%) showed immune responses, compared with 3 of the 14 (21%) patients who received the 300 μg dose. In total, MAGE-A4-specific antibody responses were induced in 5 of 21 (24%) patients. No differences in survival were seen between patients receiving the 100 μg and 300 μg doses, or between immune responders and non-responders. Eleven (50%) patients had pre-existing antibodies to NY-ESO-1. In 16 patients with esophageal or head/neck squamous cell carcinoma, the survival time was significantly shorter in those who had NY-ESO-1-co-expressing tumors. Patients with high pre-existing antibody responses to NY-ESO-1 displayed worse prognosis than those with no pre-existing response. Therefore, in planning clinical trials of MAGE-A4 vaccine, enrolling NY-ESO-1-expressing tumor or not would be a critical issue to be discussed. Combination vaccines of MAGE-A4 and NY-ESO-1 antigens would be one of the strategies to overcome the poor prognosis.
Highlights
The complex of cholesteryl pullulan (CHP) and tumor antigen consists of Cholesteryl pullulan (CHP) nanoparticles containing tumor antigen protein, and is a cancer vaccine with a novel antigen delivery system for both major histocompatibility antigen complex (MHC) class I and class II pathways [1]
While different patients responded to different antigens, each individual patient responded to the same antigens both before and after vaccination. This indicates that patients had antibodies to multiple antigens prior to CHP-melanomaassociated antigen (MAGE)-A4 vaccinations and that spreading immune reactions arose from these preexisting responses. In this phase I clinical trial, we evaluated the safety and immunogenicity of the CHP-MAGE-A4 cancer vaccine, and found that the vaccine was safe and that immune responses were induced in 24% of 21 patients with advanced cancer
We previously reported that the NY-ESO-1 protein vaccine complexed with CHP showed dose-dependent immune responses [7]
Summary
The complex of cholesteryl pullulan (CHP) and tumor antigen consists of CHP nanoparticles containing tumor antigen protein, and is a cancer vaccine with a novel antigen delivery system for both MHC class I and class II pathways [1]. Cancer-testis antigens are expressed in the normal testis and placenta, but may be expressed exclusively in tumor tissues, and as such these antigens are considered to be an ideal target for cancer immunotherapy. MAGE-A4 may be an ideal candidate as a target antigen for cancer vaccines. It has been reported that cancer-testis antigens, including the MAGE-family and NY-ESO-1 antigens, were co-expressed on the same tumor tissues [6], the clinical implication of this fact has not been well explored
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
