Division of Cancer ImmunotherapyDivision of Cancer Immunotherapy (Tsukiji)

Introduction

Member

Chief

Kiyoshi Yoshimura

Research Summary

Maintenance of laboratory on 12F of the NCC Hospital and biotherapy core facility on 6F of the NCC institute: The maintenance includes an annual checkup and repair of research instruments, the deep freezer, the freezer, the tank for liquid nitrogen and the refrigerator.

Research activities

• Development of cancer immunotherapy via chimeric antigen receptor T cell (CAR-T) therapy for targeting Molecular L against disseminated gastric cancer
• Development of CAR-T therapy for Molecular N against advanced pancreatic cancer
• Development of CAR-T therapy for Molecular G against lung cancer
• Development of CAR-T therapy for acute myeloid lymphoma
• Development of immunotherapy for solid cancers by genetically activated and invasive T cells to maximize the effect of immune checkpoint inhibitors. Elucidation of mechanism of T cell infiltration to find predictive marker for immune checkpoint inhibitors
• Pre-clinical basic research for the first-in-human (FIH) clinical trial using novel CAR-T therapy
• Research on fundamental system for cancer immune cellular therapy in clinical practice
• Development of cancer immunotherapy against malignant pleural mesothelioma using antibodies for cancer-specific antigen and CAR-T
• Establishment of novel recognition system against cancer stem cell-like cells utilizing DNA or RNA aptamer
• Phase II clinical trial for adjuvant therapy against hepatocellular carcinoma using peptide vaccine (completed)
• Doctor-led clinical trial of multiple peptides mixed vaccine targeting pediatric cancer (completed)
• Pre-clinical research for FIH clinical trial of anti-CD4 antibody therapy
• Basic research on FIH clinical trial for induced pluripotent stem cell-based T cell therapy
• Development of predictive diagnostic method for recurrent hepatocellular carcinoma using blood samples
• Study of fundamental system for new immunotherapy in clinical practice (completed)

Findings

• Molecule L expressed on the cell surface membrane expressed in gastric cancer and cancer stem cell-like cells is identified. Cytotoxic activation of CAR-T cells against the Molecule L is also confirmed.
• Molecule N expressed on the cell surface membrane expressed in pancreatic cancer and cancer stem cell-like cells is identified. The Molecule N has the possibility to influence tumor micro environment based on the proliferation tumor cells and chemokine production by the downstream of signal transaction of Molecule N. In addition, it is possibly related to a mechanism of infiltration of T cells into solid cancer.
• Molecule Y is expressed on T cell which is infiltrated into solid cancers and influences T cell activation. The Molecule Y is under study because it seems to have a direct influence on the T cell infiltration unlike regular activation of T cell which produces interferon gamma.
• Basic development of modified CAR-T cells forming activated and invasive T cells is in progress. The modified T cells will infiltrate into solid cancers and increase their number inside the cancer cell.
• Immuno-monitoring for anti GD2 antibody therapy in combination with IL-2 and CSF against refractory neuroblastoma phase I has been completed and phase II is under preparation.
• Clinical application of FITC-CAR-T therapy which was proposed by Dr. Tamada from Yamaguchi University is in progress. Our target is to apply the therapy against malignant pleural mesothelioma in two years.
• Cell processing for CD19-CAR-T therapy (phase I) was executed. The operation of the therapy was set up based on the result of the investigation on cell processing. Investigation was done by US and Australian institutions.

Clinical trials

• Cell processing after leukapheresis, preservation and immunological analysis for CD19-CAR-T therapy
• Immune-monitoring phase I for anti GD2 antibody therapy in combination with IL-2 and CSF against refractory neuroblastoma

Education

• Training a doctor on a Ph.D. course
• Training a resident physician from respiratory medicine
• Working in close coordination with other branches at the NCC hospital and having junior doctors develop a deeper understanding of immunotherapy.

Future prospects