JSCO2016: International Session 10 Recent Advances In Cancer Immunotherapy

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The 54th Annual Meeting of Japan Society of Clinical Oncology (JSCO2016)

"Renovation of Cancer Medicine in the Mature Society"



International Session 1: Lung Cancer
International Session 2: Colorectal Cancer
International Session 3: Gastric Cancer
International Session 4: Urological Cancer (Prostate and Renal Cancer)
International Session 5: Supportive Care for Adverse Events
International Session 6: Gynecological Cancer (Uterine Body Cancer and Ovarian Cancer)
International Session 7: Central Nervous System Tumor
International Session 8: New Development of Particle Beam Therapy for Cancer
International Session 9: International Cooperation in Radiation Medicine
International Session 10: Recent Advances In Cancer Immunotherapy
International Session 11: Breast Cancer
International Session 12: Pharmacology of Antitumor Agents: New Drug Application (NDA)
International Session 13: Malignant Lymphoma
International Session 14: Palliative Care
International Session 15: Radiation Therapy
International Session 16: Head and Neck Cancer
International Session 17: Skin Cancer (Malignant Melanoma)
International Session 18: Hepato-Biliary and Pancreas Cancers
International Session 19: Leukemia
International Session 20: Ethics for Clinical Research
International Session 21: Esophageal Cancer
International Session 22: Bone and Soft Tissue Tumor
FACO/JSCO Joint Symposium

Abstract Archives (in Japanese)


International Session 10: Recent Advances In Cancer Immunotherapy


Augmentation of CAR-T cell efficacy in cancer immunotherapy
Koji Tamada (Department of Immunology, Yamaguchi University Graduate School of Medicine)
Cancer immunotherapy using chimeric antigen receptor (CAR)-introduced T cells has demonstrated potent anti-tumor effects in hematological malignancies. Although CAR-T cell therapy is a promising approach in cancer immunotherapy, its efficacy against solid cancer has yet to be fully accomplished. Potential hurdles in success of CAR-T cell therapy against solid cancer include, but are not limited to 1) heterogeneous nature of solid cancers, 2) lack of appropriate target molecules, 3) immunosuppressive condition in tumor microenvironment, and 4) necessity of CAR-T cells to migrate, survive, and expand in the tumor site. In order to overcome these hurdles, we have developed next-generation CAR technology which enables CAR-T cells to simultaneously produce immuno-regulatory factors, including cytokines and chemokines, so that CAR-T cells and host immune cells efficiently accumulate, expand, and survive in microenvironment of solid tumor. These novel types of CAR-T cells (referred to as immuno-regulatory CAR-T cells) mediate potent proliferative capacity and triggers active migration of T cells and DC in vitro. Mice treated with the immuno-regulatory CAR-T cells completely rejected solid tumors, while those treated with conventional CAR-T cells were killed by tumor. Tumor tissues from the mice treated with the immuno-regulatory CAR-T cells demonstrated massive accumulation of CAR-T cells and host immune cells. Thus, we developed next-generation CAR-T cell technology which confers enhanced anti-tumor activities against solid tumors.


Clinical development of cancer immunotherapy and immunomonitoring
Shigehisa Kitano (Department of Experimental Therapeutics, National Cancer Center Hospital)
Immune checkpoint inhibitors have been the most striking among the immunotherapies under clinical development. These monoclonal antibodies (mAb) restore and augment the anti-tumor immune activities of cytotoxic T cells, mainly by blocking immune checkpoint molecules on T cells or their ligands on antigen presenting and tumor cells. The first approved immune checkpoint inhibitor was ipilimumab, a fully humanized mAb that blocks the immune suppressive signal by cytotoxic-T-lymphocyte-associated antigen 4 (CTLA-4). In 2011, the US Food and Drug Administration (FDA) approved ipilimumab for treating advanced metastatic melanoma (done in 2015 in Japan). Then, nivolumab and pembrolizumab were approved for treating advanced melanoma in 2014 and advanced non-small cell lung cancer (NSCLC) in 2015 in Japan. These humanized monoclonal antibodies block programmed cell death-1 (PD-1) protein. Nivolumab was also approved for advanced renal cell cancer treatment in August 2016 in Japan. And more, phase III trials of anti-PD-1 mAb and anti- programmed death-ligand 1 (PD-L1) mAb for head and neck cancer, ovarian cancer, bladder cancer, gastric cancer, esophageal cancer etc. are ongoing. Several clinical trials have since investigated new agents, alone and in combination, for various cancers.
As current advances in tumor immunology, the importance of the immune-suppressive cells, such as regulatory T cells (Treg), myeloid derived suppressor cells (MDSC), tumor-associated macrophages (TAM), especially in tumor microenvironment (TME) has been unveiled. Some data from basic research in mouse models and immune-monitoring data from cancer patients suggest that inhibition of the immune suppressive cells and those related cytokines etc. could activate cytotoxic T cells and infiltrate them in TME as one of the next combination strategy. The current development status and future challenges in utilizing immune checkpoint inhibitors will be presented.


Increased circulating MDSC and impact of systemic inflammation in patients with cancer
Masahiko Shibata (Department of Gastroenterological Oncology, Saitama Medical University International Medical Center)
Cancer immunotherapy has been developed and have recently recognized as one of effective treatments against cancer. Myeloid-derived suppressor cells (MDSC) is a major immune-suppressing cells appears in cancer or inflammation. To study the clinical importance of MDSC, peripheral blood was collected from the patients with gastrointestinal, ovarian, breast, thyroid and pulmonary cancers. PBMC (peripheral blood mononuclear cells) was separated using Ficoll-density gradient technique. PBMC was used for the detection of MDSC by flow cytometry (CD11b+CD14-CD33+) and cytokine-production assay in which PBMC was stimulated with PHA and 24-hour production of cytokines including IL-12, IL-10 and IL-17 were measured with ELISA. Serum concentration of IL-10 and VEGF were also measured. Circulating levels of MDSC was significantly increased in almost all types of cancer tested and these levels were significantly correlated with neutrophil/lymphocyte ratios (NLR): marker of inflammation, CRP, and inversely correlated with PHA-stimulation index (SI): marker of cell mediated immune responses, and serum concentrations of rapid-turnover protein (RTP): marker of nutrition. MDSC was also correlated with serum concentrations of IL-10 and VEGF, and production of IL-17, and inversely did to those of IL-12. The prognosis of stage IV colorectal cancer with high MDSC was significantly worse than in those with low MDSC and similar results was obtained also in gastric cancer. In thyroid cancer, MDSC was significantly higher, NLR was higher, CRP was higher and RTP was lower in patients with undifferentiated carcinoma than those with differentiated carcinoma including papillary and follicular carcinomas. Thus MDSC was increased in cancer and seemed to be correlated with immune suppression, inflammation and malnutrition. Anti-inflammatory or anti-VEGF treatment may decrease MDSC and may be effective adjuvant therapy with cancer immunotherapy.


Immunotherapy in lung cancer
Makoto Nishio (The Cancer Institute Hospital)
Recently, a second paradigm shift is occurring in treatment of advanced lung cancer.
1st paradigm shift was identification of driver mutation and introducing of the molecular target agents. 2nd paradigm shift is immunotherapy with immune checkpoint inhibition. Checkpoint inhibitors are drugs that "release the brakes" on immune cells, enabling a stronger attack against cancer. Currently, several anti-PD1antibodies such as nivolumab, Pembrolizumab and anti-PDL1antibody such as Atezolizumab, Durvalumab, Avelumab are developing.
The results of early clinical studies truly apply to the impact on treatment for NSCLC and recent Phase III studies demonstrated positive results in second line setting of NSCLC.
In addition, several combination therapies with anti-PD1/PDL1 therapy are evaluating in first line setting. Therefore, Immunotherapy may become a crucial modality for NSCLC treatment.


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