Introduction

Cancer immunotherapy is entering a new era. In 2013, Science reported cancer immunotherapy as the breakthrough of the year. Clinical trials of immune-checkpoint inhibitors and T cells expressing genetically engineered receptors (so-called chimeric antigen receptors/T-cell receptors) have shown dramatic efficacy in cancer patients. These promising results have promoted the further development of cancer immunotherapies as potential cancer treatments.
In our laboratory, we have been developing various novel cancer immunotherapies based on our original research for use in adoptive cell therapy, as cancer vaccines, and more recently, for exosome (EV) therapy.
One cancer immunotherapy approach is adoptive cell transfer of antigen-specific T cells. A promising strategy for creating usable cancer-specific T-lymphocytes is genetic engineering of T cell receptor (TCR) genes in patient lymphocytes. We are currently conducting clinical trials of adoptive cell therapy using T cells that target cancer-testis antigens, such as NY-ESO-1 and MAGE-A4. With this strategy, these are also an opportunity to extend the applications of adoptive T cell therapy to patients with other cancers that express these antigens. An alternative approach is the preparation of cancer-specific chimeric antigen receptors (CAR). We are currently developing a novel CAR construct that targets peptide-MHC complexes and other cell surface antigens with rigid specificity and strong efficacy.
Another cancer immunotherapy approach involves the use of cancer vaccines, and vaccines aimed at controlling cancer have been constructed using a variety of formulations, such as peptides, proteins, nucleic acids, or cells, with an aim to sensitize or activated cancer-reactive T cells.
For use in cancer vaccines and other biomedical applications, we have developed a series of nano-sized hydrogel particles (nanogels) to create novel nano-materials. One particular material, cholesteryl pullulan (CHP), a pullulan polysaccharide that is partially hydrophobized through chemical modification with cholesteryl groups, forms nanogel particles with a diameter of ~50 nm. CHP efficiently forms stable complexes with polypeptides, and fabrication of these CHP-polypeptide complexes is feasible, simple, and reproducible. These features make it an ideal nano-particulate carrier for the delivery of polypeptide-based therapeutic molecules. Therefore, we have been developing novel cancer vaccines with this CHP-polypeptide complex.
Although these two approaches, adoptive cell transfer and vaccination, have been major developmental focuses of our original cancer immunotherapy research, more recently, we have begun to develop novel cancer therapies using extracellular vesicles (EVs). In our laboratory, we study EVs derived from CD8+ T cells, with an emphasis on the suppression of cancer infiltration and metastasis.

Professor and Chairman
Hiroshi Shiku, M.D.