• Title, Summary, Keyword: tumor immunotherapy

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Immature thymocyte antigen, JL1, as a possible immunodiagnostic and immunotherapeutic target for leukemia

  • Shin, Young Kee;Choi, Eun Young;Kim, Seok Hyung;Park, Seong Hoe
    • IMMUNE NETWORK
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    • v.1 no.1
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    • pp.1-6
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    • 2001
  • The identification of tumor-specific antigens has represented a critical milestone in cancer diagnosis and therapy. Clinical research in this area for leukemia has also been driven over the past few decades by the hope that surface antigens with restricted tissue expression would be identified. Disappointingly, only a small number of the leukemic antigens identified to date, meet sufficient criteria to be considered viable immunophenotypic markers. In this paper, we nominate anti-JL1 monoclonal antibody as an immunodiagnostic and immunotherapeutic candidate for leukemia. The JL1 molecule appears to be a novel cell surface antigen, which is strictly confined to a subpopulation of limited stages during the hematopoietic differentiation process. Despite the restricted distribution of the JL1 antigen in normal tissues and cells, anti-JL1 monoclonal antibody specifically recognizes various types of leukemia, irrespective of immunophenotypes. On the basis of these findings, we propose JL1 antigen as a tumor-specific marker, which shows promise as a candidate molecule for diagnosis and immunotherapy in leukemia, and one that spares normal bone marrow stem cells.

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Dendritic Cells-based Vaccine and Immune Monitoring for Hepatocellular Carcinoma

  • Lee, Dae-Heui
    • The Korean Journal of Physiology and Pharmacology
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    • v.14 no.1
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    • pp.11-14
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    • 2010
  • Human tumors, including those of the hepatobiliary system, express a number of specific antigens that can be recognized by T cells, and may provide potential targets for cancer immunotherapy. Dendritic cells (DCs) are rare leucocytes that are uniquely potent in their ability to capture, process and present antigens to T cells. The ability to culture sufficient numbers of DCs from human bone marrow or blood progenitors has attracted a great deal of interest in their potential utilization in human tumor vaccination. $CD34^+$ peripheral blood stem cells (PBSCs) were obtained from a patient with a hepatocellular carcinoma. The PBSCs were cultured in the X-VIVO 20 medium supplemented with the Flt-3 Ligand (FL), GM-CSF, IL-4 and TNF-$\alpha$ for 12 days. The morphology and functions of the cells were examined. The generated cells had the typical morphology of DCs. When the DCs were reinjected into the same patient, an augmentation of the cytotoxic T lymphocyte (CTL) activity was observed. Concomitantly, an increase in the natural killer (NK) cell activity was also detected in the patient. These results suggest that DCs-based cancer immunotherapy may become an important treatment option for cancer patients in the future.

Oncolytic Vaccinia Virus Expressing 4-1BBL Inhibits Tumor Growth by Increasing CD8+ T Cells in B16F10 Tumor Model

  • Lee, Na-Kyung;Kim, Hong-Sung
    • Biomedical Science Letters
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    • v.18 no.3
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    • pp.210-217
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    • 2012
  • Oncolytic viral vectors have shown good candidates for cancer treatment but have many limitations. To improve the therapeutic potential of oncolytic vaccinia virus, we developed a recombinant vaccinia virus expressing the 4-1BBL co-stimulatory molecule or CCL21. 4-1BBL and CCL21 expression was identified by FACS analysis and immunoblotting. rV-4-1BBL vaccination shows significant tumor regression compared to rV-LacZ, but rV-CCL21 shows rapid tumor growth compared to rV-LacZ in the poorly immunogenic B16 murine melanoma model. 4-1BBL expression resulted in the increase of the number of CD8+ T cells and especially the increase of effector (CD62L-CD44+) CD8+ T cells. These data suggest 4-1BBL may be the potential target for enhancement of tumor immunotherapy.

Assessment of Relationship between Wilms' Tumor Gene (WT1) Expression in Peripheral Blood of Acute Leukemia Patients and Serum IL-12 and C3 Levels

  • Rezai, Omran;Khodadadi, Ali;Heike, Yuji;Mostafai, Ali;Gerdabi, Nader Dashti;Rashno, Mohammad;Abdoli, Zahra
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.16
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    • pp.7303-7307
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    • 2015
  • Background: Leukemia is a common cancer among children and adolescents. Wilms' tumor gene (WT1) is highly expressed in patients with acute leukemia. It is found as a tumor associated antigen (TAA) in various types of hematopoietic malignancies and can be employed as a useful marker for targeted immunotherapy and monitoring of minimal residual disease (MRD). In this regard, WT1 is a transcription factor that promotes gene activation or repression depending on cellular and promoter context. The purpose of this study was assessment of WT1 gene expression in patients with acute leukemia, measurement of IL-12 and C3 levels in serum and evaluation of the relationship between them. Materials and Methods: We evaluated the expression of WT1 mRNA using real-time quantitative RT-PCR and serum levels of IL-12 and C3 using ELISA and nephelometry in peripheral blood of 12 newly diagnosed patients with acute leukemia and 12 controls. Results: The results of our study showed that the average wT1 gene expression in patients was 7.7 times higher than in healthy controls (P <0.05). In addition, IL-12 (P = 0.003) and C3 (P <0.0001) were significantly decreased in the test group compared to controls. Conclusions: WT1 expression levels are significantly higher in patients compared with control subjects whereas serum levels of interleukin-12 and C3 are significantly lower in patients. Wt1 expression levels in patients are inversely related with serum levels of IL-12 and C3.

T Cell-directed Immunotherapeutic Approaches for Head and Neck Squamous Cell Carcinoma (두경부편평세포암에서의 T세포 면역치료)

  • Choi, Yoon Seok
    • Korean Journal of Head & Neck Oncology
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    • v.33 no.1
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    • pp.7-13
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    • 2017
  • Despite improved treatment outcomes of locally advanced disease over the last 2 decades, the survival of patients with recurrent and/or metastatic head and neck squamous cell carcinoma (HNSCC) remains dismal. There is a clear need for development of novel therapeutic strategies for recurrent and/or metastatic HNSCC. Recent advances in understanding tumor immunology have been directly and rapidly translated into clinical success of T cell-directed immunotherapeutic approach in the treatment of several types of solid cancers. Among them, impact of immune checkpoint inhibition using neutralizing antibodies is the most striking. A variety of immunotherapeutic strategies targeting T cells have been also studied in HNSCC, especially in recurrent and/or metastatic setting even with significant survival benefit. The present article reviews the basic concept of T cell-directed immunotherapy and the current status of such approaches in the treatment of HNSCC.

Expression of Cancer-Testis Antigens in Pediatric Cancers

  • Ghafouri-Fard, Soudeh
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.13
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    • pp.5149-5152
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    • 2015
  • Cancer-testis antigens (CTAs) are a group of tumor-associated antigens with more than 140 members whose expression has been shown to be limited to gametogenic tissues and placenta among normal tissues. However, malignant tissues of different origins have shown aberrant and elevated expression of these antigens. Such a pattern of expression endows beneficial properties for use as cancer biomarkers as well as immunotherapeutic targets as a result of the immune-privileged status of the testes. CTAs have been shown to be expressed in pediatric brain tumors, different types of sarcomas, leukemias, and lymphomas as well as neuroblastomas. Although data regarding their expression pattern in childhood tumors are not as comprehensive as for adult tumors, it is supposed that CTA-based immunotherapeutic approaches can also be used for pediatric cancers. However, there are limited data about the objective clinical responses following immunotherapy in such patients. Here we try to review the available information.

Current Approaches in Development of Immunotherapeutic Vaccines for Breast Cancer

  • Allahverdiyev, Adil;Tari, Gamze;Bagirova, Melahat;Abamor, Emrah Sefik
    • Journal of Breast Cancer
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    • v.21 no.4
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    • pp.343-353
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    • 2018
  • Cancer is the leading cause of death worldwide. In developed as well as developing countries, breast cancer is the most common cancer found among women. Currently, treatment of breast cancer consists mainly of surgery, chemotherapy, hormone therapy, and radiotherapy. In recent years, because of increased understanding of the therapeutic potential of immunotherapy in cancer prevention, cancer vaccines have gained importance. Here, we review various immunotherapeutic breast cancer vaccines including peptide-based vaccines, whole tumor cell vaccines, gene-based vaccines, and dendritic cell vaccines. We also discuss novel nanotechnology-based approaches to improving breast cancer vaccine efficiency.

Effects of the ex-vivo Immunotherapy on the Mammary Gland Tumorigenesis Induced by 7, 12-dimethylbenz[a]anthracene(DMBA) in rats (7, 12-dimethylbenz[a]anthracene(DMBA) 투여에 의한 랫드 유선암 모델에서 ex-vivo 면역치료 효과)

  • 정자영;김옥희;이영순
    • Toxicological Research
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    • v.14 no.4
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    • pp.465-474
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    • 1998
  • This study was examined on the effect of ex-vivo immunotherapy in 7, 12-dimethylbenz[a]anthracene (DMBA)-induced rat mammary carcinogenesis. Sprague-Dawley female 40 rats were divided into Jour groups. As a positive control, Group I was intubated with DMBA, 5 mg /100 g body weight and single dose, at experimental onset. Group II was treated ex-vivo immunotherapy with polyinosinic-polycytidylic acid (Poly I : C) and Group III was treated with Interleukin-2 (IL-2). Group IV was negative control. All rats were sacrificed at 16 weeks after DMBA intubation. Mammary gland wet weight, dry fat free tissue weight, incidence of tumor, and the number of lobules, alveolar buds, terminal end buds, and terminal ducts were examined. Morphological changes of the mammary gland after treated with DMBA were analyzed by whole mount and histopathological method. As results, the induced mammary tumors of Group I, II and III were 60%, 33% and 0%, respectively. Histopathological types of induced-mammary tumors were adenoma, adenocarcinoma and carcinosarcoma. In analysis of the whole mount method, the number of the terminal end buds, terminal ducts and lobules were significantly lower in Group II (p<0.01) and III (p<0.01) than DMBA alone treated Group I. In microscopic observation, hyperplastic alveolar nodules were significantly lower in Group III than Group I (p<0.01). In conclusion, IL-2 had strong inhibitory effect on the mammary gland tumorigenesis induced by DMBA in rats. Whole mount method may be a useful technique to assess the mammary carcinogenesis. Moreover, hyperplastic alveolar nodules were very sensitive parameter to assess the mammary carcinogenesis.

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Enhanced macrophage uptake of radiolabeled liposome triggered by ginseng extracts

  • Lee, Woonghee;Rhee, Man Hee;Yoo, Jeongsoo
    • Journal of Radiopharmaceuticals and Molecular Probes
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    • v.5 no.2
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    • pp.113-119
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    • 2019
  • During tumor progression various immunosuppressive cells are recruited to a tumor microenvironment (TME). Tumor-associated macrophages (TAMs) are particularly abundant in TME. Based on their function, macrophages are categorized into two phenotypes: tumoricidal M1 and tumor-supportive M2. Generally, TAMs closely resemble M2-macrophages and lead to tumor growth. However, their phenotype can be changed by immune activator from M2 to M1 and thus promote tumor immunotherapy. Ginseng extracts are well known for its anti-tumor and anti-inflammatory effects from numerous reported studies. However, the mechanism of their effects is still not clear. Recently, some studies suggested that ginseng extracts induced immune activation as well as anti-tumor activities by a repolarization of activated macrophage from M2 phenotype to M1 phenotype. But, further verification about the mechanism as to how ginseng extracts can stimulate the immune response is still needed. In this study, we investigated whether ginseng extracts can alter the phenotype from M2 macrophages to M1 macrophages in mice by using a radiolabeled liposome. And we also evaluated the potential of radiolabeled liposome as a nuclear imaging agent to monitor the transition of phenotype of TAMs. In conclusion, the ginseng extracts seem to change the phenotype of macrophages from M2 to M1 like as lipopolysaccharide (LPS) in mice.

Current Status of Immunotherapeutic Strategies for Central Nervous System Tumors

  • Yang, Meng-Yin;Khan-Farooqi, Haumith;Prins, Robert M.;Liau, Linda M.
    • Journal of Korean Neurosurgical Society
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    • v.40 no.4
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    • pp.217-226
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    • 2006
  • Malignant gliomas are the most common type of primary brain tumor and are in great need of novel therapeutic approaches. Advances in treatment have been very modest, significant improvement in survival has been lacking for many decades, and prognosis remains dismal. Despite "gross total" surgical resections and currently available radio-chemotherapy, malignant gliomas inevitably recur due to reservoirs of notoriously invasive tumor cells that infiltrate adjacent and non-adjacent areas of normal brain parenchyma. In principle, the immune system is uniquely qualified to recognize and target these infiltrative pockets of tumors cells, which have generally eluded conventional treatment approaches, In the span of the last 10 years, our understanding of the cancer-immune system relationship has increased exponentially; and yet we are only beginning to tease apart the intricacies of the central nervous system and immune cell interactions. This article reviews the complex associations of the immune system with brain tumors. We provide an overview of currently available treatment options for malignant gliomas, existing gaps in our knowledge of brain tumor immunology, and strategies that might be exploited for improved design of "custom immunotherapeutics." We will also examine major new immunotherapy approaches that are being actively investigated to treat patients with malignant glioma, and identify some current and future research priorities in this area.