- MeSH
- Hypersensitivity MeSH
- BCG Vaccine MeSH
- Immunity, Cellular MeSH
- Mice MeSH
- Tuberculin MeSH
- Vaccination MeSH
- Animals MeSH
- Check Tag
- Mice MeSH
- Animals MeSH
- MeSH
- Immunization methods MeSH
- Immunosuppression Therapy MeSH
- Mice MeSH
- Nematode Infections immunology MeSH
- Check Tag
- Mice MeSH
- Publication type
- Comparative Study MeSH
Renal cell carcinoma (RCC) is one of the most lethal urologic malignancies. Its incidence continues to rise worldwide with a rate of 2% per year. Approximately, one-third of the RCC patients are diagnosed at advanced stages due to the asymptomatic nature of its early stages. This represents a great hurdle, since RCC is largely chemoresistant/radioresistant, and targeted therapy of mRCC still has limited efficacy. The 5-year survival rate of metastatic RCC (mRCC) is only around 10%. Adoptive cell transfer (ACT), a particular form of cell-based anticancer immunotherapy, is a promising approach in the treatment of mRCC. The vaccination principle, however, faces unique challenges that preclude the efficacy of ACT. In this article, we review the main challenges of ACT in the treatment of mRCC and describe multiple methods that can be used to overcome these challenges. In this respect, the ultimate purpose of this review is to provide a descriptive tool by which to improve the development of novel protocols for ACT of mRCC.
- MeSH
- Immunotherapy methods MeSH
- Carcinoma, Renal Cell pathology MeSH
- Humans MeSH
- Survival Rate MeSH
- Kidney Neoplasms pathology MeSH
- Adoptive Transfer methods MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
Adoptivní imunoterapie pomocí antivirových T lymfocytů (AVT) získaných od zdravých dárců je jedním z moderních přístupů, považovaných za průlom v léčbě refrakterních a závažných virových infekcí, které často doprovázejí primární imunodeficity nebo alogenní transplantaci krvetvorných kmenových buněk. Souhrnné sdělení popisuje téměř 30letý vývoj AVT proti lidskému cytomegaloviru, viru Epsteina a Barrové, lidskému adenoviru a lidskému polyomaviru BK. V článku jsou, přiblíženy základní metodické přístupy k jejich výrobě a charakterizovány výsledky získané v klinických studiích, které ověřily bezpečnost a účinnost postupu. Současný vývoj naznačuje, že léčba virových infekcí pomocí zmrazených AVT uložených v bankách by se v budoucnu mohla stát běžně dostupnou terapeutickou modalitou.
Adoptive immunotherapy using antiviral T cells (AVT) obtained from healthy donors is one of the advanced approaches considered as a breakthrough in the treatment of refractory and severe viral infections that often accompany primary immunodeficiencies or allogeneic hematopoietic stem cell transplantations. The review describes nearly 30 years of the development of AVT to human cytomegalovirus, Epstein-Barr virus, human adenovirus, and human polyomavirus BK. The review introduces the basic methodological approaches to their production and summarizes the results from clinical studies that tested the safety and efficiency of the procedures used. Recent studies indicate that the treatment of viral infections by frozen AVT stored in banks could become a commonly available therapeutic modality.
- MeSH
- T-Cell Antigen Receptor Specificity MeSH
- Transplantation, Homologous MeSH
- Immunotherapy, Adoptive * methods MeSH
- Humans MeSH
- Adoptive Transfer MeSH
- Stem Cell Transplantation * MeSH
- Virus Diseases pathology therapy MeSH
- Check Tag
- Humans MeSH
- Publication type
- Research Support, Non-U.S. Gov't MeSH
Snahou jednotlivých imunoterapeutických postupů je namíření imunitních reakcí organismu proti nádorové tkáni tak, aby vedly k eliminaci nebo ke kontrole růstu maligně transformovaných buněk. Jednou z možností imunoterapie je využití adoptivního T-buněčného transferu, jehož podstatou je aplikace ex vivo upravených a expandovaných tumor specifických lymfocytů , které rozeznávají a ničí neoplastické buňky. Úspěšnost adoptivní T-buněčné terapie se významně zlepšila pochopením základních molekulárních mechanismů interakce imunitního systému s nádory. Slibných výsledků bylo dosaženo zejména u klinických studií s maligním melanomem, karcinomem ledviny a lymfatické leukemie. Adoptiv- ní T-buněčná terapie se v současnosti postupně etabluje mezi nadějné imunoterapeutické postupy a rozšiřuje tak portfolio léčebných možností. Cílem tohoto článku je podat stručné informace o teoretických předpokladech protinádorové imunoterapie a zároveň shrnout poznatky z oblasti výzkumu a aplikace imunoterapie se zaměřením na adoptivní T-buněčný transfer.
The aim of current immunotherapeutic approaches is to elicit an individual's immune response towards a tumor tissue to eliminat e or, at least, to control proliferation of the neoplastic tumor cells. Among the contemporary cancer treatment strategies, the adoptive T cell transfer shows to be the most progressively developing method that uses an ex vivo modified and expanded tumor-specific T cells as a tool to target and destroy the neoplastic tumor cells. The efficacy of the adoptive T cell therapy has significantly improved in recent years due to a bet ter understanding of the molecular mechanisms that control the interactions of immune system and tumor cells. Promising results have already been achieved within the clinical trials of malignant melanoma, renal ca ncer and lymphoid leukemia. The adoptive T cell therapy is therefore gradually finding its stable place among the other contemporary immunotherapeutic strategies and expands the spectrum of available treatment options in cancer therapy. The purpose of this review is to introduce a theoretical background of the cancer treatment strategies and also to summarize the contemporary status of the adoptive T cell transfer therapy and its prospects for future.
- Keywords
- protinádorová imunita, adoptivní T-buněčný transfer, tumor specifické lymfocyty,
- MeSH
- Adaptive Immunity immunology MeSH
- Immunotherapy, Adoptive * methods statistics & numerical data trends MeSH
- Clinical Trials as Topic MeSH
- Humans MeSH
- Neoplasms * immunology therapy MeSH
- T-Lymphocytes immunology MeSH
- Lymphocytes, Tumor-Infiltrating immunology MeSH
- Check Tag
- Humans MeSH
Cílem imunoterapie je využití imunitních mechanizmů k eliminaci nebo ke kontrole růstu maligně transformovaných buněk. Jednou z možností imunoterapie je aplikace adoptivního transferu lymfocytů T, jehož podstatou je infuze ex vivo expandovaných tumor specifických lymfocytů, které rozeznávají a ničí neoplastické buňky. Úspěšnost adoptivní T buněčné terapie se významně zlepšila pochopením základních molekulárních mechanizmů interakce imunitního systému s nádory. Slibných výsledků bylo dosaženo zejména u maligního melanomu, karcinomu ledviny a lymfatické leukemie. Adoptivní T buněčná terapie se postupně etabluje mezi nadějné imunoterapeutické postupy a rozšiřuje tak portfolio léčebných možností, i když pro svoji metodickou náročnost nenašla dosud velké rozšíření.
The aim of current immunotherapeutic approaches is to harness the individual's immune system towards a tumor tissue to eliminate or, at least, to control proliferation of the neoplastic cells. Among the cancer treatment strategies, the adoptive T cell transfer is progressively developing method that uses an ex vivo modified and expanded tumor-specific T cells as a tool to target and destroy the neoplastic tumor cells. The efficacy of the adoptive T cell therapy has significantly improved in recent years due to a better understanding of the molecular mechanisms that control the interactions of immune system and tumor cells. Promising results have already been achieved within the clinical trials in malignant melanoma, renal cancer and lymphoid leukemia. The adoptive T cell therapy is therefore gradually finding its place among the other immunotherapeutic strategies and expands the spectrum of available treatment options in cancer therapy.
- Keywords
- protinádorová imunita, adoptivní transfer lymfocytů T, tumor specifické lymfocyty, expandované lymfocyty T periferní krve,
- MeSH
- Antigens, Neoplasm immunology MeSH
- CD4-Positive T-Lymphocytes immunology transplantation MeSH
- T-Lymphocytes, Cytotoxic immunology MeSH
- Immunotherapy, Adoptive * MeSH
- Humans MeSH
- Melanoma immunology therapy MeSH
- Skin Neoplasms immunology therapy MeSH
- Neoplasms * immunology therapy MeSH
- Cancer Vaccines MeSH
- T-Lymphocytes immunology MeSH
- Lymphocytes, Tumor-Infiltrating * MeSH
- Check Tag
- Humans MeSH
- Publication type
- Research Support, Non-U.S. Gov't MeSH
Adoptive T cell transfer has been shown to be an effective method used to boost tumor-specific immune responses in several types of malignancies. In this study, we set out to optimize the ACT protocol for the experimental treatment of prostate cancer. The protocol includes a pre-stimulation step whereby T cells were primed with autologous dendritic cells loaded with the high hydrostatic pressure-treated prostate cancer cell line, LNCaP. Primed T cells were further expanded in vitro with anti-CD3/CD28 Dynabeads in the WAVE bioreactor 2/10 system and tested for cytotoxicity. Our data indicates that the combination of pre-stimulation and expansion steps resulted in the induction and enrichment of tumor-responsive CD4(+) and CD8(+) T cells at clinically relevant numbers. The majority of both CD4(+) and CD8(+) IFN-γ producing cells were CD62L, CCR7 and CD57 negative but CD28 and CD27 positive, indicating an early antigen experienced phenotype in non-terminal differentiation phase. Expanded T cells showed significantly greater cytotoxicity against LNCaP cells compared to the control SKOV-3, an ovarian cancer line. In summary, our results suggest that the ACT approach together with LNCaP-loaded dendritic cells provides a viable way to generate prostate cancer reactive T cell effectors that are capable of mounting efficient and targeted antitumor responses and can be thus considered for further testing in a clinical setting.
- MeSH
- Lymphocyte Activation MeSH
- Antigens, Neoplasm immunology MeSH
- Bioreactors MeSH
- Dendritic Cells immunology MeSH
- Epitopes, T-Lymphocyte immunology MeSH
- Immunotherapy, Adoptive methods MeSH
- Interferon-gamma biosynthesis immunology MeSH
- Humans MeSH
- Cell Line, Tumor MeSH
- Prostatic Neoplasms immunology MeSH
- Ovarian Neoplasms immunology MeSH
- T-Lymphocytes, Regulatory immunology MeSH
- Case-Control Studies MeSH
- T-Lymphocyte Subsets immunology MeSH
- T-Lymphocytes immunology MeSH
- Check Tag
- Humans MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
