Global Development of CHP Cancer Protein Vaccines

Clinical Development of CHP-NY-ESO-1

CHP means Cholesteryl hydrophobized pullulan, in which pullulan, a polysaccharide existing in the nature, is modified with cholesterol to add hydrophobicity. Under the physiological condition, it spontaneously forms nano-sized spherical particles. The CHP can form complexes with various proteins. It was found that the immunization with antigen protein complexed with CHP simultaneously activated both antigen-specific killer and helper T cells and elicited anti-tumor immunity more potently and efficiently than the immunization with protein alone. If immunization is performed with protein alone without CHP, that vaccination activated only helper T cells and caused a weak anti-tumor immune response. Thus it was confirmed that CHP protein complex technology to activate both killer and helper T cells is very promising as a new vaccine technology. After a large body of basic experiments, CHP-HER2 complex vaccine using a recombinant protein of HER2, one of the famous human cancer-associated antigen proteins, was evaluated in the clinical researches in Japan. As a result, the safety and capability of this vaccine to induce antigen specific immune responses was clearly confirmed.

NY-ESO-1 protein is one of the cancer/testis antigens which are expressed mainly in testis among normal tissues and is expressed specifically and highly in a wide range of human cancers. In addition to HER2 antigen, this very famous, highly immunogenic protein NY-ESO-1 was newly employed for the target antigen used in CHP protein cancer vaccine. A Japanese clinical investigational research of CHP-NY-ESO-1 vaccine was then conducted by the investigators of Okayama Univ. and Osaka Univ., and in this trial, the capability of CHP-NY-ESO-1 to induce antigen-specific immune responses was clearly confirmed. Interestingly, some clinical responses were also observed in some of esophageal cancer patients joined to this trial. Based on these results obtained in the preclinical and clinical studies of CHP protein complex vaccines, ImmunoFrontier decided to intensively develop the CHP-NY-ESO-1 vaccine. The phase I clinical trial of CHP-NY-ESO-1 vaccine will be started in the US from 2008. On the other hands, the phase I and phase IIa clinical trials for esophageal cancer in Japan will be also started as the investigator-initiated trial supported by the Ministry of Education, Culture, Sports, Science and Technology as a Japanese national project “Cancer Translational Research (TR) Program”.

Clinical Development of CHP-MAGE-A4

MAGE-A4 is also one of the cancer/testis antigens and is expressed in a broad range of cancers especially in intractable cancers including lung, esophageal, and head and neck cancers. Clinical development ofCHP-MAGE-A4, a vaccine with the combination of MAGE-A4 and CHP, is now planned for the treatment of non small cell lung cancer as a target disease. The clinical trial of this vaccine will be started in the US in 2009.

Research and Development for New CHP Protein Vaccines

CHP protein vaccines can be applicable to a various kinds of cancers by changing antigen proteins to be employed, enabling us to efficiently create new pipelines. We also intend to obtain antigen proteins with cancer specific expression and high immunogenicity in order to generate new CHP cancer protein vaccines. This will be accomplished by utilizing our own unique technologies and our established cooperation with worldwide research networks in the field of cancer immunity.

Creation of Next Generation Protein Drugs by Applying CHP

By applying CHP to the delivery of protein drugs, we intend to enhance the performance of protein drugs and to create next generation protein drugs with reduced burden of patients.