• Title, Summary, Keyword: tumor immunotherapy

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Immunotherapy in Head and Neck Squamous Cell Cancer

  • Denaro, Nerina;Merlano, Marco Carlo
    • Clinical and Experimental Otorhinolaryngology
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    • v.11 no.4
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    • pp.217-223
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    • 2018
  • Prognosis in relapsed metastatic head and neck squamous cell cancer (RM-HNSCC) is dismal. Platinum based chemotherapy in combination with Cetuximab is used in first-line setting, while no further validated options are available at progression. Immunotherapy has produced durable clinical benefit in some patients with RM-HNSCC although the premises are several patients are nonresponders. Studies are ongoing to determine predictive factors and the ideal setting/combination of novel immunotherapies. In this paper, we discuss the past and present of immunotherapy in head and neck cancer and provide an up-to-date information regarding the potential ways to improve immunotherapy outcomes in HNSCC.

Tumor Immunology and Immune Checkpoint Inhibitors in Non-Small Cell Lung Cancer

  • Jung, Chi Young;Antonia, Scott J.
    • Tuberculosis and Respiratory Diseases
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    • v.81 no.1
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    • pp.29-41
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    • 2018
  • Lung cancer is one of the most commonly diagnosed cancers and the leading cause of cancer-related deaths worldwide. Although progress in the treatment of advanced non-small cell lung cancer (NSCLC) has been made over the past decade, the 5-year survival rate in patients with lung cancer remains only 10%-20%. Obviously, new therapeutic options are required for patients with advanced NSCLC and unmet medical needs. Cancer immunotherapy is an evolving treatment modality that uses a patient's own immune systems to fight cancer. Theoretically, cancer immunotherapy can result in long-term cancer remission and may not cause the same side effects as chemotherapy and radiation. Immunooncology has become an important focus of basic research as well as clinical trials for the treatment of NSCLC. Immune checkpoint inhibitors are the most promising approach for cancer immunotherapy and they have become the standard of care for patients with advanced NSCLC. This review summarizes basic tumor immunology and the relevant clinical data on immunotherapeutic approaches, especially immune checkpoint inhibitors in NSCLC.

Induction of 90K-specific Cytotoxic T Lymphocytes for Colon Cancer Immunotherapy

  • Lee, Ji-Hee;Park, Myung-Suk;Chung, Ik-Joo
    • IMMUNE NETWORK
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    • v.10 no.6
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    • pp.206-211
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    • 2010
  • Background: Dendritic cell (DC)-based tumor vaccine is an attractive modality for the treatment of colon cancer because it has been recurred and produced few side effects in patients. Secretory glycoprotein 90K has been found at elevated level in various cancer tissues and sera. We investigated to establish a more effective DC vaccine for the treatment of colon cancer in which the levels of 90K are elevated. Methods: We obtained the concentrated 90K from 293T cells stably expressing 90K. DCs were cultured from peripheral blood monocytes, and a DC vaccine pulsed with tumor lysate was compared with a DC vaccine pulsed with 90K. We measured the functional activity for CTLs by using IFN-${\gamma}$-enzyme linked immunoabsorbent spot (ELISPOT) assay. Results: DCs pulsed with tumor lysate+90K exhibited the enhanced T cell stimulation, polarization of $\ddot{i}$ T cell toward Th1. The CTLs generated by DCs pulsed with 90K efficiently lysed HCT116 cells. The results indicate that 90K-speicifc-CTLs can recognize 90K proteins naturally presented by colon cancer cells. Conclusion: Our study suggests that 90K-specific CTLs generated by 90K-pulsed DCs could be useful effector cells for immunotherapy in colon cancer.

B Cells Transduced with HPV16 E6/E7-expressing Adenoviral Vector Can Efficiently Induce CTL-dependent Anti-Tumor Immunity

  • Kim, Yun-Sun;Ko, Hyun-Jeong;Kim, Yeon-Jeong;Han, Seung-Hee;Lee, Jung-Mi;Chang, Woo-Sung;Jin, Hyun-Tak;Sung, Young-Chul;Kang, Chang-Yuil
    • IMMUNE NETWORK
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    • v.7 no.3
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    • pp.109-116
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    • 2007
  • Background: Human papillomavirus (HPV) infection is responsible for cervical cancer, a common cancer in women. Since HPV infection and cancer development are controlled by the host immune system, immunotherapy against HPV can be helpful in preventing or treating HPV-associated cervical cancer. Two oncoproteins of HPV16, E6 and E7, are promising targets for immunotherapy against cervical cancer, because they are constitutively expressed in cervical cancer. Methods: Since cellular vaccines using B cells as well as dendritic cells offer an efficient approach to cancer immunotherapy, we opted to use B cells. We evaluated the immunogenicity and anti-tumor effects of a B cell vaccine transduced with HPV16 E6/E7-expressing adenovirus. Results: Vaccination with HPV16 E6/E7-transduced B cells induced E6/E7-specific $CD8^+$ T cell-dependent immune responses and generated anti-tumor effects against E6/E7-expressing TC-1 tumor. The anti-tumor effect induced by this B cell vaccine was similar to that elicited by DC vaccine, showing that B cells can be used as an alternative to dendritic cells for cellular vaccines. Conclusion: Thisstudy has shown the feasibility of using B cells as immunogenic APCs and the potential for developing prophylactic and therapeutic vaccines against HPV-associated cervical cancer using a B cell vaccine transduced with adenovirus expressing HPV16 E6/E7.

Anti-tumor Efficacy of a Hepatocellular Carcinoma Vaccine Based on Dendritic Cells Combined with Tumor-derived Autophagosomes in Murine Models

  • Su, Shu;Zhou, Hao;Xue, Meng;Liu, Jing-Yu;Ding, Lei;Cao, Meng;Zhou, Zhen-Xian;Hu, Hong-Min;Wang, Li-Xin
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.5
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    • pp.3109-3116
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    • 2013
  • The majority of hepatocellular carcinoma (HCC) patients have a poor prognosis with current therapies, and new approaches are urgently needed. We have developed a novel therapeutic cancer vaccine platform based on tumor cell derived autophagosomes (DRibbles) for cancer immunotherapy. We here evaluated the effectiveness of DRibbles-pulsed dendritic cell (DC) immunization to induce anti-tumor immunity in BALB/c mouse HCC and humanized HCC mouse models generated by transplantation of human HCC cells (HepG2) into BALB/c-nu mice. DRibbles were enriched from H22 or BNL cells, BALB/c-derived HCC cell lines, by inducing autophagy and blocking protein degradation. DRibbles-pulsed DC immunization induced a specific T cell response against HCC and resulted in significant inhibition of tumor growth compared to mice treated with DCs alone. Antitumor efficacy of the DCs-DRibbles vaccine was also demonstrated in a humanized HCC mouse model. The results indicated that HCC/DRibbles-pulsed DCs immunotherapy might be useful for suppressing the growth of residual tumors after primary therapy of human HCC.

Immunotherapy for Non-Small Cell Lung Cancer

  • Yoon, Sung Ho
    • Tuberculosis and Respiratory Diseases
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    • v.77 no.3
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    • pp.111-115
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    • 2014
  • Lung cancer is the leading cause of cancer-related mortality worldwide, and more than 80% of cases are of non-small cell lung cancer. Although chemotherapy and molecularly targeted therapy may provide some benefit, there is a need for newer therapies for the treatment of patients with advanced NSCLC. Immunotherapy aims to augment the recognition of cancer as foreign, to stimulate immune responsiveness, and to relieve the inhibition of the immune response that allows tolerance to tumor survival and growth. Two immunotherapeutic approaches showing promise in NSCLC are immune checkpoint inhibition and cancer vaccination. Although currently immunotherapy does not have an established role in the treatment of NSCLC, these patients should be enrolled in formal clinical trials.

Efficient Interleukin-21 Production by Optimization of Codon and Signal Peptide in Chinese Hamster Ovarian Cells

  • Cho, Hee Jun;Oh, Byung Moo;Kim, Jong-Tae;Lim, Jeewon;Park, Sang Yoon;Hwang, Yo Sep;Baek, Kyoung Eun;Kim, Bo-Yeon;Choi, Inpyo;Lee, Hee Gu
    • Journal of Microbiology and Biotechnology
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    • v.29 no.2
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    • pp.304-310
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    • 2019
  • Interleukin-21 is a common ${\gamma}$-chain cytokine that controls the immune responses of B cells, T cells, and natural killer cells. Targeting IL-21 to strengthen the immune system is promising for the development of vaccines as well as anti-infection and anti-tumor therapies. However, the practical application of IL-21 is limited by the high production cost. In this study, we improved IL-21 production by codon optimization and selection of appropriate signal peptide in CHO-K1 cells. Codon-optimized or non-optimized human IL-21 was stably transfected into CHO-K1 cells. IL-21 expression was 10-fold higher for codon-optimized than non-optimized IL-21. We fused five different signal peptides to codon-optimized mature IL-21 and evaluated their effect on IL-21 production. The best result (a 3-fold increase) was obtained using a signal peptide derived from human azurocidin. Furthermore, codon-optimized IL-21 containing the azurocidin signal peptide promoted $IFN-{\gamma}$ secretion and STAT3 phosphorylation in NK-92 cells similar to codon-optimized IL-21 containing original signal peptide. Collectively, these results indicate that codon optimization and azurocidin signal peptides provide an efficient approach for the high-level production of IL-21 as a biopharmaceutical.

Effect of Dendritic Cell Based Cancer Vaccine Using Allogeneic Tumor Cell Lysate in Melanoma Pulmonary Metastasis Model (동종 종양 세포 용해액을 이용한 수지상 세포 항암 백신의 흑색종 폐암 전이 모델에서의 효과 연구)

  • Lee, Young-Joon;Kim, Myung-Joo;In, So-Hee;Choi, Ok-Mi;Baek, So-Young;Kwon, Young-Do;Lee, Hyun-Ah
    • IMMUNE NETWORK
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    • v.5 no.3
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    • pp.163-171
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    • 2005
  • Background: To perform the successful dendritic cell-based cancer immunotherapy one of the main issues to be solved is the source of antigen for DC pulsing. Limitations occur by using auto-tumor lysate due to the difficulties obtaining enough tumor tissue(s) quantitatively as well as qualitatively. In this study the possibility of allogeneic tumor cell lysate as a DC pulsing antigen has been tested in mouse melanoma pulmonary me tastasis model. Methods: B16F10 melanoma cells $(1{\timeS}10^5/mouse)$ were inoculated intra venously into the C57BL/6 mouse. Therapeutic DCs were cultured from the bone marrow myeloid lineage cells with GM-CSF and IL-4 (1,000 U/ml each) for 7 days and pulsed with lysate of either autologous B16F10 (B-DC), allogeneic K1735 (C3H/He origin; K-DC) or CloneM3 (DBA2 origin; C-DC) melanoma cells for 18 hrs. Pulsed-DCs $(1{\times}10^6/mouse)_{[CGP1]}$ were injected i.p. twice with one week interval starting from the day 1 after tumor cell inoculation. Results: Without observable toxicity, allogeneic tumor cell lysate pulsed-DC induced the significantly better anti-tumor response (tumor scale: $2.7{\pm}0.3,\;0.7{\pm}0.3\;and\;0.3{\pm}0.2$ for saline, B-DC and C-DC treated group, respectively). Along with increased tumor specific lymphocyte proliferations, induction of IFN-${\gamma}$ secretion against both auto- and allo-tumor cell lysates was observed from the DC treated mice. (w/B16F10-lysate: $44.97{\pm}10.31,\;1787.94{\pm}131.18,\;1257.15{\pm}48.27$, w/CloneM3 lysate: 0, $1591.13{\pm}1.83,\;1460.47{\pm}86.05pg/ml$ for saline, B-DC and C-DC treated group, respectively) Natural killer cell activity was also increased in the mice treated with tumor cell lysate pulsed-DC ($8.9{\pm}_{[CGP2]}0.1,\;11.6{\pm}0.8\;and\;12.6{\pm}0.7%$ specific NK activity for saline, B-DC and C-DC treated group, respectively). Conclusion: Conclusively, promising data were obtained that allogeneic-tumor cell lysate can be used as a tumor antigen for DC-based cancer immunotherapy.

Immunostimulation Activity of the Crude Polysaccharides Fractionated from Eleutherococcus senticosus, and its Application to Prevent of Tumors by Combination Therapy with Cisplatin (오가피로부터 분리된 조다당 분획물의 면역자극활성 및 Cisplatin과의 병용에 의한 항암 상승작용의 유도)

  • 하은숙;황수현;유광원;신광순;조형민;김창한;박우문;윤택준
    • YAKHAK HOEJI
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    • v.47 no.3
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    • pp.159-166
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    • 2003
  • In order to study the clinical usefulness of crude polysaccharides fractionated from Eleutherococcus senticosus, EN-3, in eliminating tumors, we have investigated the effect of combination therapy on the murine tumor metastasis and growth models. In experimental metastasis of colon26-M3.1 cells, prophylactic intravenous (i.v.) administration of EN-3 (0.5, 5, and 50 $\mu\textrm{g}$/mouse) inhibited tumor metastasis compared with tumor control group in 33.6, 66.8, and 81.8% respectively. The administration of EN-3 (50 $\mu\textrm{g}$/mouse) also exhibited a 66.1% therapeutic effect on lung tumor metastasis. Although EN-3 induced no toxic effect on both tumor cell and normal splenocyte in the concentration below 100 $\mu\textrm{g}$/mι in in vitro, it induced significant proliferating activity on normal splenocyte in the concentration-dependent manner. In an analysis of NK-cell activity, i.v. administration of EN-3 (4∼100 $\mu\textrm{g}$/mouse) significantly augmented NK cytotoxicity to YAC-1 tumor cells. The combination treatments of cisplatin (10 $\mu\textrm{g}$) and EN-3 (5 $\mu\textrm{g}$) induced synergistic effect on the inhibition of tumor metastasis in experimental tumor metastasis model produced by colon26-M3.1 cells. In addition, the combination treatments also exhibited prolongation of lifespan in S∼180 tumor bearing mouse for over the 60 days. Even though cisplatin (2.5 $\mu\textrm{g}$/mι) exhibited cytotoxicity to tumor cells and inhibited tumor growth over 95% in in vitro, combination treatment with EN-3 (20 $\mu\textrm{g}$/mι) was induced splenocyte proliferation and produced cytokines, such as TNF-$\alpha$, IL-1 and IL-12, from the macrophages. These results suggested that EN-3 stimulate immune system non-specifically and apply to the biological response modifiers (BRM) in chemo-immunotherapy for tumor prevention.

The Prospective of Antigen-presenting Cells in Cancer Immunotherapy (항원제시세포를 이용한 암 치료제 개발전망)

  • Shim Doo-Hee;Lee Jae-Hwa
    • KSBB Journal
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    • v.19 no.6
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    • pp.415-420
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    • 2004
  • All around the world, the rate of attack of cancer diseases has been going up and the number of cancer patients has been increasing every year. Cancer can be divided into malignant tumor and benign tumor according to its growth appearance. Many studies and experiments have been conducted and the various treatment are being created to find the way to care malignant. Dendritic cells (DCs), which is an agent of cancer treatments by using an immune reaction in our body, plays an important role to present by a tumor antigen to cytotoxic T-cell and help them to attack the tumor cell directly. However there are some defects of this therapy. Soluble human leukocyte antigen-immunoglobulin fusion protein (HLA-Ig) based artificial antigen presenting cell (aAPC) as the antigen presenting cell (APC) which is complement and overcome some of the limitations of dendritic cell-based vaccines and ex vivo expansion of human T cells is new method for cancer therapy. In this article, we are reviewing the role of DCs and the treatment with it, and searching for the possibility of the new development of immunotherapy for cancer.