Nihon Rinsho. Japanese Journal Of Clinical Medicine[JOURNAL]
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200 papers
[Dendritic cell vaccines loaded with autologous tumor lysates for solid tumors].
Kamigaki T, Takahara M, Teruya T
Nihon Rinsho · 2017 Feb · PMID 30562866
Recently, immunotherapy has been utilized as a novel option for the treatment of various malignancies, however, it is necessary to develop immune cell therapy on the basis of the blockade of immune checkpoints, antigen p...
Recently, immunotherapy has been utilized as a novel option for the treatment of various malignancies, however, it is necessary to develop immune cell therapy on the basis of the blockade of immune checkpoints, antigen presentation on dendritic cell (DC) vaccines and the high avidity tumor reactive T cells. Autologous tumor lysate-loaded DC vaccines could have a potency to elicit T cells immune response with both epitopes of neoantigen and com- mon antigen; however the innate immunity should be essential for the cross-presentation process. Furthermore, DC vaccines loaded with tumor lysates by electroporation system eli- cited both antigen-specific CD8 and CD4 T cells. In order to break the immunosuppression, the combined therapy of the tumor lysate-loaded DC vaccines and immune checkpoint inhib- itors should be investigated in the future.
[Chimeric antigen receptor (CAR)-T cell therapy].
Sakoda Y, Tamada K
Nihon Rinsho · 2017 Feb · PMID 30562865
Chimeric antigen receptor (CAR)-T cell therapy, where patients' own T cells are engi- neered to express receptor that targets antigen found on the surface of cancer cells, delivers outstanding efficacy to treat hematolog...
Chimeric antigen receptor (CAR)-T cell therapy, where patients' own T cells are engi- neered to express receptor that targets antigen found on the surface of cancer cells, delivers outstanding efficacy to treat hematological malignancies. This personalized medicine has been actively explored by researchers in academia and quickly developed for clinical applica- tion by several pharmaceutical/biotech companies. While CAR-T cell therapy is a highly promising technology, many challenges remain to be overcome in targeting solid tumors, in- cluding on-target off-tumor toxicity, inefficient accumulation and survival of CAR-T cells in the immunosuppressive tumor microenvironment. In this review, we briefly describe the cur- rent status, challenges, and future perspectives of CAR-T cell therapy.
[Gene-modified T cell therapy].
Ikeda H
Nihon Rinsho · 2017 Feb · PMID 30562864
Immune checkpoint inhibitor therapy has achieving a sensational success in the treatment of patients with progressive cancers. However, the efficacy remains as 10-30% of the pa- tients in most type of cancers, suggesting...
Immune checkpoint inhibitor therapy has achieving a sensational success in the treatment of patients with progressive cancers. However, the efficacy remains as 10-30% of the pa- tients in most type of cancers, suggesting that the development of new treatments for pa- tients resistant to the therapy is an important challenge of the field. It is likely that the patients without the induction of tumor-specific lymphocytes in the body will not respond to immune checkpoint inhibitor. Therefore, adoptive cell therapy with gene-modified tumor- specific T cells will be one promising treatment of the patients resistant to checkpoint inhibitor therapy. This review summarizes the recent progress in the clinical development of gene- modified T cell therapy and discusses the issues that should be improved in the near future.
[Development of next-generation peptide vaccination therapy].
Tsukahara T, Hirohashi Y, Emori M … +1 more , Torigoe T
Nihon Rinsho · 2017 Feb · PMID 30562863
Identification of tumor-associated antigens (TAAs) recognized by T cells has enabled clinical peptide vaccination trials targeting TAAs to be performed for patients with carcinoma or sarcoma. Although peptide vaccination...
Identification of tumor-associated antigens (TAAs) recognized by T cells has enabled clinical peptide vaccination trials targeting TAAs to be performed for patients with carcinoma or sarcoma. Although peptide vaccination could elicit specific immunological responses, clinical objective responses were not frequently observed, especially in end-stage patients with large tumor burdens who were receiving high-dose chemotherapy. The key points for developing effective peptide vaccination therapy are (i) targeting cancer stem-like cell antigens that are expressed in cancer cells but not in normal cells and regulating tumorigenesis and (ii) manip- ulating memory T stem cells that have the capacity of long-living and resistance to chemo- therapeutic drugs. The combination of a peptide vaccination and immune checkpoint inhibi- tors might also be attractive.
[WT1 peptide cancer vaccine].
Sugiyama H
Nihon Rinsho · 2017 Feb · PMID 30562862
Wilms'tumor gene 1(WT1) is a leukemia cell-specific marker, and WT1 protein is pan- tumor-associated antigen (TAA) that was ranked as a top among 75 TAAs. WT1 peptide vaccine has been performing for over 800 patients wit...
Wilms'tumor gene 1(WT1) is a leukemia cell-specific marker, and WT1 protein is pan- tumor-associated antigen (TAA) that was ranked as a top among 75 TAAs. WT1 peptide vaccine has been performing for over 800 patients with 58 kinds of malignancies including leukemia and various types of solid tumors. Clinical results are promising, and adverse effects are limited to skin eruption on the vaccine injection sites. Two types of WT1 peptide vaccines are under clinical studies by pharmaceutical companies for the development of medicine.
[Cancer peptide vaccine targeted glypican-3 antigen].
Nakatsura T
Nihon Rinsho · 2017 Feb · PMID 30562861
We identified glypican-3 (GPC3) as a carcinoembryonic antigen would be an ideal target for hepatocellular carcinoma (HCC) immunotherapy. We identified HLA-A24- and A2-restricted GPC3-derived peptides that can induce GPC3...
We identified glypican-3 (GPC3) as a carcinoembryonic antigen would be an ideal target for hepatocellular carcinoma (HCC) immunotherapy. We identified HLA-A24- and A2-restricted GPC3-derived peptides that can induce GPC3-reactive CTLs but not autoimmunity. In a phase I using this peptide vaccine in patients with advanced HCC, we collected evidence of immune responses, antitumor effects, and the safety. We could detect peptide-specific CTLs in the peripheral blood of most patients, and established a lot of peptide-specific CTL clones from PBMCs and tumor of patients vaccinated. In a phase II as an adjuvant therapy for HCC patients, it improved the 1-y recurrence rate in patients with GPC3-positive tumors. GPC3 is overexpressed in ovarian clear cell carcinoma, hepatoblastoma, and so on. GPC3 peptide vac- cine or GPC3 peptide specific TCR-T cell therapy has hope for treatment or prevention of these GPC3-positive cancers.
[Personalized peptide vaccine for cancer treatment; now and its future].
Waki K, Yamada A
Nihon Rinsho · 2017 Feb · PMID 30562860
Therapeutic cancer vaccines have been dramatically progressing in a variety of their forms for the last two decades. The CTIepitope peptide vaccines are one of them. We proposed the personalized peptide vaccine (PPV) the...
Therapeutic cancer vaccines have been dramatically progressing in a variety of their forms for the last two decades. The CTIepitope peptide vaccines are one of them. We proposed the personalized peptide vaccine (PPV) therapy. Our PPV is different from the classical one in that a maximum of four peptides are selected based on the patient's HLA-A types and.their pre-existing immunity (=immunological memory), leading to the more rapid and stronger re- sponses to the vaccinated peptides. Since then, we have been conducting clinical studies for various types of advanced cancers. We summarized the clinical outcomes of the PPV studies and described its prospect for the clinical application.
[The development status of the next-generation immune checkpoint inhibitors].
Fuse M, Yoshimura K
Nihon Rinsho · 2017 Feb · PMID 30562859
Recently immune checkpoint inhibitors such as anti-CTLA-4, PD-1 and PD-L1 blocking antibodies have been developed resulting in the dramatic change of standard-of-care in can- cer treatment. Furthermore, in phase 3 study...
Recently immune checkpoint inhibitors such as anti-CTLA-4, PD-1 and PD-L1 blocking antibodies have been developed resulting in the dramatic change of standard-of-care in can- cer treatment. Furthermore, in phase 3 study of nivolumab plus ipilimumab for metastatic malignant melanoma, the combination therapy prolonged progression-free survival and im- proved objective response rate, showing the promising activity of the combination therapy with immune checkpoint inhibitors. On the other hand, the frequencies of immune related adverse events increased. Now new immune checkpoint inhibitor is expected to develop so as to substitute for these or to be used with combination. Here we will address the mecha- nism and the function of Lag-3, TIGIT and Tim-3 that are expected as immune checkpoint inhibitors.
[Immune checkpoint (PD-1 and CTIA-4) signal inhibitors for gynecologic oncology; up to date].
Hamanishi J, Mandai M, Konishi I
Nihon Rinsho · 2017 Feb · PMID 30562858
Gynecological malignances include cervical, uterine (sarcoma), ovarian, vaginal, and vulvar cancers are among the most common cancers in women. Advanced and recurrent cases of these malignancies have poor prognosis and h...
Gynecological malignances include cervical, uterine (sarcoma), ovarian, vaginal, and vulvar cancers are among the most common cancers in women. Advanced and recurrent cases of these malignancies have poor prognosis and hence new types of treatment strategy are ur- gently required. Recent clinical trials have revealed an outstanding anti-tumor effect of im- mune checkpoint inhibitors (anti-cytotoxic T-lymphocyte-associated protein 4 [CTIA-4] anti- body, anti- programmed cell death 1 [PD-1] antibody and/or anti-PD-Li [PD-i ligand 1] antibody) in patients with gynecologic malignancies, especially for ovarian cancer and endo- metrial cancer. Besides, several clinical trials for other gynecologic malignancie's also have started and achieved a certain result in these agents and demonstrated some'candidates of predictive biomarkers of anti-tumor response such as polymerase epsilon (POLE) ultra- mutated or DNA mismatch repair deficiency-mutated genes in endometrial cancer and ovar- ian cancer. In this review, we highlight recent clinical trials that evaluated immune check- point inhibitors against gynecologic malignancies and discuss the clinical perspectives and issues regarding immune checkpoint inhibitors.
[Immunotherapy for gastroenterological cancer].
Narita Y, Muro K
Nihon Rinsho · 2017 Feb · PMID 30562857
After the paradigm shift happened in malignant melanoma, the immune checkpoint inhibi- tors have been developed all over the world in the many types of cancer not the exception of the gastroenterological cancer. The auth...
After the paradigm shift happened in malignant melanoma, the immune checkpoint inhibi- tors have been developed all over the world in the many types of cancer not the exception of the gastroenterological cancer. The authors showed a comprehensive review of the literature and update on the use of anti-CTLA-4, anti-PD-1 and anti-PD-LI therapy in the area of gastro- enterological cancer. The clinical evidence of the immune checkpoint inhibitors in gastroen- terological cancer remains limited, although the light come in this cancer type and immuno- therapy could play an important role in the year to come.
[Treatment of lung cancer using immune checkpoint inhibitors].
Shiraishi H, Ohe Y
Nihon Rinsho · 2017 Feb · PMID 30562856
The treatment strategy of lung cancer is now significantly changing by the appearance of immune checkpoint inhibitors. Although anti-programmed cell death-1 (PD-1) antibody agents, nivolumab and pembrolizumab, have been...
The treatment strategy of lung cancer is now significantly changing by the appearance of immune checkpoint inhibitors. Although anti-programmed cell death-1 (PD-1) antibody agents, nivolumab and pembrolizumab, have been already adopted as standard treatments in second line treatment of non-small-cell lung cancer, optimal use is essential due to the high costs and serious adverse effects. Therefore, further investigation of predictive markers in immune checkpoint blockade is ongoing, but robust one has not yet been identified. On the other hand, many clinical trials are now in progress regarding other immune checkpoint in- hibitors, combination therapy with cytotoxic or molecular target agents, different treatment settings and so on.
[Melanoma].
Uhara H
Nihon Rinsho · 2017 Feb · PMID 30562855
Since 2011, several effective drugs for patients with metastatic melanoma, including the BRAF inhibitors, the MEK inhibitors and the immune checkpoint inhibitors, have been ap- proved. Ipilimumab, nivolumab and the combi...
Since 2011, several effective drugs for patients with metastatic melanoma, including the BRAF inhibitors, the MEK inhibitors and the immune checkpoint inhibitors, have been ap- proved. Ipilimumab, nivolumab and the combination have shown response rates of 10-20%, 20-40% and up to 60% and a median progression-free survival of 2, 7 and 12 months, respec- tively. The management of immune related toxicities is keypoint for adequate use of these agents.
[Basic and clinical evaluation of anti-CCR4 mAb in cancer immunotherapy].
Oka M, Kurose K
Nihon Rinsho · 2017 Feb · PMID 30562854
CCR4 is one of the receptors for chemokines and is expressed on Th2, Th17, skin-homing T cells and regulatory T cells (Tregs). Activated Tregs highly express CCR4 and are induced into tumor environment by M2 macrophages-...
CCR4 is one of the receptors for chemokines and is expressed on Th2, Th17, skin-homing T cells and regulatory T cells (Tregs). Activated Tregs highly express CCR4 and are induced into tumor environment by M2 macrophages-producing CCL22. Tregs show strong suppres- sive functions in cancer immunity, resulting in tumor progression. On the other hand, moga- mulizumab is a humanized anti-human CCR4 monoclonal antibody with a defucosylated Fe region which markedly enhances ADCC activity, and the antibody has been shown to effi- ciently deplete CCR4-positive cells. Therefore, a phase Ia clinical study of mogamulizumab was conducted in the treatment of solid cancers. Mogamulizumab almost depeleted activated Tregs in peripheral blood, and then re-activated CTL function with low grade of adverse events. However, no clinical responses were observed in ten patients. A phase lb study is now on-going, and further clinical studies may be needed in combination with other anti- tumor drugs.
[Anti-PD-1 antibody and anti-PD-Li antibody -from basic and clinic-].
Kitano S
Nihon Rinsho · 2017 Feb · PMID 30562853
Immune checkpoint inhibitors are most striking among the clinical development of immu- notherapy. These monoclonal antibodies (mAb) restore and augment the anti-tumor immune activities of cytotoxic T cells by mainly bloc...
Immune checkpoint inhibitors are most striking among the clinical development of immu- notherapy. These monoclonal antibodies (mAb) restore and augment the anti-tumor immune activities of cytotoxic T cells by mainly blocking immune checkpoint molecules on T cells or their ligands on antigen presenting and tumor cells. Based on preclinical data, many clinical trials have demonstrated the acceptable safety profiles and efficacies in a variety of cancers. Nivolumab and pembrolizumab, humaznized monoclonal antibodies which block pro- grammed death-1 (PD-1) molecule, were approved for advanced melanoma in 2014 and for advanced NSCLC in 2015 and 2016 in Japan. And, nivolumab was also done for advanced re- nal cell cancer and Hodgkin lymphoma in Japan in 2016. And more, phase III trials of anti-PD- 1 mAb and anti-PD-Li mAb for head and neck cancer, ovarian cancer, bladder cancer, gastric cancer, esophageal cancer etc. are ongoing. Several clinical trials have investigated new agents, alone and in combination, for various cancers. In this chapter the history of development of immne checkpoint inhibitors from basic re- search to clinical trial is overviewed.
[CTIA-4 blockade therapy; biology and clinical activity].
Tada K, Heike Y
Nihon Rinsho · 2017 Feb · PMID 30562852
Cytotoxic T lymphocyte antigen-4 (CTLA-4) is a key inhibitory regulator for priming phase in T cell adaptive immunity against cancer. CTLA-4 blockade monotherapy or combination therapy with PD-1 blockade induces T cell a...
Cytotoxic T lymphocyte antigen-4 (CTLA-4) is a key inhibitory regulator for priming phase in T cell adaptive immunity against cancer. CTLA-4 blockade monotherapy or combination therapy with PD-1 blockade induces T cell activation and shows clinical activity in melanoma patients. Anti-CTLA-4 antibody is the first drug for immune checkpoint blockade and has been clinically used over the past decades. Several clinical characteristics and biomarkers in cancer immunotherapy were identified during developing CTLA-4 blockade therapy for mela- noma patients. Further roles of CTLA-4 blockade in other cancers are still to be determined. Well-designed clinical trial considering immune biology and findings from translational re- search is warranted to emerge potential efficacy of CTLA-4 blockade in cancer treatment.
[Cancer immunotherapy targeting neoantigens derived from tumor-specific gene mutations].
Sasada T
Nihon Rinsho · 2017 Feb · PMID 30562851
Cancer immunotherapies targeting "tumor-associated antigens" derived from wild-type proteins have shown limited success in clinical trials to date. Recent development of next generation sequencing and bioinformatics tech...
Cancer immunotherapies targeting "tumor-associated antigens" derived from wild-type proteins have shown limited success in clinical trials to date. Recent development of next generation sequencing and bioinformatics technology has allowed identification of "neoanti- gens" derived from genetic alterations, such as mutations, insertions, and deletions, re- stricted to tumor cells. Tumor-specific neoantigens, but not tumor-associated antigens, can be recognized as "foreign" by the host immune system. Therefore, they might show higher immunogenicity and more efficiently activate anti-tumor immune responses capable of con- trolling tumor burden. In this review article, I have summarized and discussed clinical signifi- cance of tumor-specific neoantigens and their potential clinical application for personalized cancer immunotherapies.
[Regulatory T cells: A target in anticancer immunotherapy].
Enokida T, Nishikawa H
Nihon Rinsho · 2017 Feb · PMID 30562850
Regulatory T cells (Tregs) expressing the transcription factor Foxp3 play a crucial role in maintaining peripheral immune tolerance and preventing autoimmunity. With being abun- dant in tumor tissue, they promote tumor p...
Regulatory T cells (Tregs) expressing the transcription factor Foxp3 play a crucial role in maintaining peripheral immune tolerance and preventing autoimmunity. With being abun- dant in tumor tissue, they promote tumor progression by suppressing effective antitumor im- munity. Additionally, recent progresses suggest that Tregs comprise functionally distinct subsets and contribute differently to cancer prognosis. Thus, there has been considerable interest in integration of strategies restricting Tregs-mediated immune suppression by selec- tively reducing Tregs or attenuating their suppressive activity with activating tumor-specific effector T cells. Understanding mechanisms for abundance of Tregs in tumors is crucial for developing optimal Tregs-mediated immunotherapy.
[Recent progress of cancer immunology and immunotherapy].
Kawakami Y
Nihon Rinsho · 2017 Feb · PMID 30562849
Cancer immunotherapy began as a Coley's vaccine, and then, non-specific immuno- modulators, anti-tumor monoclonal antibody, cytokines, cancer vaccine (e.g. tumor antigens, dendritic cells, modified cancer cells), adoptiv...
Cancer immunotherapy began as a Coley's vaccine, and then, non-specific immuno- modulators, anti-tumor monoclonal antibody, cytokines, cancer vaccine (e.g. tumor antigens, dendritic cells, modified cancer cells), adoptive cell therapy (e.g. TIL, TCR/CAR-T cells), and immune-checkpoint inhibitors (PD-1/PD-Li, CTLA4 blocking antibody) have been developed and evaluated in clinical trials. The last two immunotherapies have recently shown durable clinical effects even in the patients with advanced cancers. Progress of human cancer immu- nology has been made along with the development of immunotherapy. Particularly, the anal- ysis of clinical trials of the recent immune-checkpoint inhibitors resulted in the understand- ing of human cancer immune-environments. Further investigation with multi-omics and immunological studies will lead to development of more effective cancer immunotherapy.
A new self-completing questionnaire for motor and non-motorsymptoms in Parkinson's disease (MASAC-PD31).
Takahashi H
Nihon Rinsho · 2017 Jan · PMID 30566311
Parkinson's disease (PD) patients may suffer from various motor symptoms as well as non-motor symptoms. In order to identify and grade these symptoms within the limited time in outpatient clinic, a new self-completing qu...
Parkinson's disease (PD) patients may suffer from various motor symptoms as well as non-motor symptoms. In order to identify and grade these symptoms within the limited time in outpatient clinic, a new self-completing questionnaire (MASAC-PD31) was developed. The questionnaire consists of two parts. Part 1 consist of 14 questions related to motor symptoms and activities of daily living (ADL) during both "on" and "off" periods. Part 2 consist of 17 questions related to non-motor symptoms, such as sleep disturbances, autonomic dysfunction, cognition, mood, fatigue, smell and sexual problem. Correlations of the scores on the MASAC-PD31 with other clinical scales, such as modified H & Y stage, UPDRS, PDQ-39, Schwab & England ADL scale and were previously evaluated and MASAC-PD31 was shown to be valid and reliable scale. The questionnaire can als6 be used as a tool to identify clinically unrecognized symptoms which lead to" better management of PD.
Japan Parkinson's Progression Markers Initiative (J-PPMI).
Mukai Y, Murata M
Nihon Rinsho · 2017 Jan · PMID 30566310
Pathological changes of Parkinson's disease begin before the advent of motor symptoms. At the onset of Parkinson's disease (PD), already half of dopaminergic neurons are degenerated. It is useful to reveal the time cours...
Pathological changes of Parkinson's disease begin before the advent of motor symptoms. At the onset of Parkinson's disease (PD), already half of dopaminergic neurons are degenerated. It is useful to reveal the time course in the prodromal PD in order to establish the early diagnosis markers and the modifying therapies for PD. The Japan Parkinson's Progression Markers Initiative (J-PPMI) is longitudinal, multi-center study to assess the progression of clinical features, imaging and biological markers in the prodromal phase of synucleinopathy (PD, Lewy body dementia and multiple system atrophy). Subjects of J-PPMI are patients with the rapid eye movement sleep behavior disorder (RBD) which is known as a high risk factor for the development of Parkinson's disease.
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