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CHP Technology and Its Application to Cancer Protein Vaccines

 CHP is short for Cholesteryl Hydrophobized Pullulan. Pullulan, a natural polysaccharide, is chemically modified with cholesterol to add hydrophobicity. CHP forms spherical particles of nanometer size by self-organization under the physiological condition (see Fig. A). CHP particle can contain various substances in it and especially, it is a very unique material excellent in embedding proteins. While CHP has an action to help stabilization and folding of proteins by this nature, It showed a very interesting nature when CHP was applied to vaccination with protein antigens. That is the finding that when antigen proteins are immunized in the form of complex with CHP, reaction of both killer and helper T cells specific to the antigen proteins is strongly and simultaneously activated.
 As it is well known in the field of vaccine that when immunization is made only with proteins alone, only helper T cells are usually activated, resulting in vaccines of lower performance, the fact that antigen proteins administered as a complex with CHP could activate both antigen-specific killer and helper T cells attracted wide attention. At the same time, it was a great discovery that made us to decide the R&D of CHP cancer protein vaccines. The mechanism that antigen protein can activate both killer and helper T cells when immunized in a form of complex with CHP is now under investigation in detail. The outline is illustrated in Fig. B.

Fig. A
 
Fig. B

 We think that CHP cancer protein vaccines utilizing the unique features of CHP can be unusually high performance vaccines, and we are promoting eagerly to put them into practical use. And, as mentioned above, CHP has an action to enhance in vitro and in vivo stabilization of proteins contained in it. By utilizing this function, we are trying to create next generation protein-based drugs that have improved the weakness of conventional ones.

 On the other hand, concerning the antigen proteins to be employed for CHP protein vaccines, we have a policy to employ not peptides but full length or fragment with certain length of proteins. The reason is as follows;

・ Full length or fragment with certain length of proteins can include multiple epitopes (epitopes are the amino acid sequences that recognized by immune cells and antibodies). So the vaccine with such protein can be recognized by both killer and helper T cells. In this point, simultaneous activation of killer and helper T cells is achieved.
・ Most of human cells express histocompatibility antigen (HLA). HLA is a molecule necessary for an immunological process so called antigen presentation. In this process, HLA forms complexes with epitope peptides derived from antigen proteins and is expressed on cell surface to present epitopes to T cells. While there is differences in the type of HLA among individuals, which is attributable to individual differences in immune responses. Full length or fragment with certain length of proteins can contain multiple epitopes for various types of HLA. Consequently, cancer vaccines which employ full length or fragment with certain length of proteins can be used as universal therapeutics which do not select patients.

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