Division of Cancer Immunotherapy (Tsukiji Campus)

Kiyoshi Yoshimura, Shigehisa Kitano, Tetsuhiko Asao, Ayumu Itou, Yonju Kimu, Moeko Inoue, Masanori Fuse, Rie Ishibashi, Shino Hirose, Manami Kobayashi

Introduction

The Division of Cancer Immunotherapy aims to develop novel cancer immunotherapy and apply it for clinical trials by advancing immunological monitoring system, i.e. finding a biomarker to predict the efficacy and side effect of the treatment.

Our team and what we do

• Development of active tumor-infiltrating T cell therapy for solid cancer in order to maximize the effect of immune checkpoint inhibitors
• Study of Wnt/β-catenin dependent/independent T cell infiltrating mechanism to identify predictive marker for immune checkpoint inhibitors
• Research on fundamental systems for cancer immunotherapy in clinical practice
• Immunological monitoring for domestic clinical development on ch14.18 immunotherapy using IL2. CSF targeting refractory neuroblastoma
• Immunological monitoring of gastric and ovarian cancer ascetic fluid for GAPFREE
• Development of cancer immunotherapy via chimeric antigen receptor T cell (CAR-T) therapy targeting Molecule L on gastric, pancreatic, colorectal, and lung cancers
• Development of improved CAR-T therapy with a new mechanism for solid cancer
• Development of cancer immunotherapy via CAR-T therapy targeting Molecule N on gastric and pancreatic cancers
• Development of CAR-T therapy for AML
• Cell handling after apheresis, preservation, and immunological review for CD19 CAR-T therapy

Research activities

• Identification of membrane surface protein Molecule N expressed commonly on pancreatic cancer and pancreatic cancer stem cell like cells
  >>>Molecule N works as a downstream intracellular signal molecule and has an impact on tumor growth and chemokine-mediated tumor microenvironment. It is possible that Molecule N is related to T cell infiltration into solid cancer.
• Identification of a) Molecule Y which expressed on T cells infiltrating into solid cancer and b) its role in T cell activation
  >>>Molecule Y is highly expected to be related with the infiltrative mechanism other than enhancing T cell activation.
• Development of cancer immunotherapy targeting signal 3 by a) researching active tumor-infiltrating T cells and b) revealing the mechanism.
• Immunological monitoring of gastric and ovarian cancer ascetic fluid for GAPFREE
• dentification of a) membrane surface protein Molecule L expressed commonly on gastric cancer and gastric cancer stem cell like cells and b) strong cytotoxic activation of CAR-T

Clinical trials

• Phase I: Cell processing for CD19 CAR-T therapy
  >>>Creation of a framework of laboratory after facility audit by the U.S., Australian, and European institutions
• Phase II study: immunological monitoring for domestic clinical development on ch14.18 immunotherapy using IL2. CSF targeting refractory neuroblastoma

Education

• Training a resident physician from respiratory medicine
  >>>Manuscript is in preparation
• Training five doctors in Yamaguchi University Ph.D. course
  >>>One has received Ph.D. and an encouraging award from Yamaguchi University School of Medicine for his manuscript which has been accepted by Cancer Science. He is nominated for the Young Investigator Award.
  >>>One's manuscript has been accepted and waiting for publication.
  >>>One's manuscript is under review.
  >>>The other two are engaged in research.
• The researcher in the lab was awarded with best speech at the Japan Society of Clinical Oncology.
• Working in close coordination with other branches at the National Cancer Center Hospital (NCCH), and having junior doctors develop a deeper understanding for immunotherapy.

Future prospects

While the target is mostly Signal 1 or Signal 2 in the mainstream of immunotherapy, we plan to analyze the immune activation mechanism targeting Signal 3. In addition, we will also continue the analysis on the mechanism of T cell infiltration into solid cancer cell. It will be an innovative breakthrough once the mechanism is fully understood.

Our three major goals for 2017 are a) further development of our current study on novel immunotherapy based on tumor immune mechanism, b) publishing papers on our findings, and c) acquisition of large budget.

List of papers published in 2016

Journal

1.Yamamoto S, Suga K, Maeda K, Maeda N, Yoshimura K, Oka M. Breast sentinel lymph node navigation with three-dimensional computed tomography-lymphography: a 12-year study. Breast Cancer, 23:456-462, 2016

2.Matsukuma S, Yoshimura K, Ueno T, Oga A, Inoue M, Watanabe Y, Kuramasu A, Fuse M, Tsunedomi R, Nagaoka S, Eguchi H, Matsui H, Shindo Y, Maeda N, Tokuhisa Y, Kawano R, Furuya-Kondo T, Itoh H, Yoshino S, Hazama S, Oka M, Nagano H. Calreticulin is highly expressed in pancreatic cancer stem-like cells. Cancer Sci, 107:1599-1609, 2016