共查询到20条相似文献,搜索用时 15 毫秒
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Yee C 《Journal of translational medicine》2005,3(1):17
Adoptive T cell therapy involves the ex vivo selection and expansion of effector cells for the treatment of patients with
cancer. In this review, the advantages and limitations of using antigen-specific T cells are discussed in counterpoint to
vaccine strategies. Although vaccination strategies represent more readily available reagents, adoptive T cell therapy provides
highly selected T cells of defined phenotype, specificity and function that may influence their biological behavior in vivo.
Adoptive T cell therapy offers not only translational opportunities but also a means to address fundamental issues in the
evolving field of cancer immunotherapy. 相似文献
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Cellular therapies have shown increasing promise as a cancer treatment. Encouraging results against hematologic malignancies are paving the way to move into solid tumors. In this review, we will focus on T-cell therapies starting from tumor infiltrating lymphocytes (TILs) to optimized T-cell receptor-modified (TCR) cells and chimeric antigen receptor-modified T cells (CAR-Ts). We will discuss the positive preclinical and clinical findings of these approaches, along with some of the persisting barriers that need to be overcome to improve outcomes. 相似文献
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Tumors originate from a number of genetic events that deregulate homeostatic mechanisms controlling normal cell behavior. The immune system, devoted to patrol the organism against pathogenic events, can identify transformed cells, and in several cases cause their elimination. It is however clear that several mechanisms encompassing both central and peripheral tolerance limit antitumor immunity, often resulting into progressive diseases. Adoptive T‐cell therapy with either allogeneic or autologous T cells can transfer therapeutic immunity. To date, genetic engineering of T cells appears to be a powerful tool for shaping tumor immunity. In this review, we discuss the most recent achievements in the areas of suicide gene therapy, and TCR‐modified T cells and chimeric antigen receptor gene‐modified T cells. We provide an overview of current strategies aimed at improving the safety and efficacy of these approaches, with an outlook on prospective developments. 相似文献
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Background
Adoptive transfer of tumor infiltrating or circulating lymphocytes transduced with tumor antigen receptors has been examined in various clinical trials to treat human cancers. The tumor antigens targeted by transferred lymphocytes affects the efficacy of this therapeutic approach. Because cancer stem cells (CSCs) play an important role in tumor growth and metastasis, we hypothesized that adoptive transfer of T cells targeting a CSC antigen could result in dramatic anti-tumor effects.Results
An EpCAM-specific chimeric antigen receptor (CAR) was constructed to transduce human peripheral blood lymphocytes (PBLs) and thereby enable them to target the CSC marker EpCAM. To investigate the therapeutic capabilities of PBLs expressing EpCAM-specific CARs, we used two different tumor models, PC3, the human prostate cancer cell line, which has low expression levels of EpCAM, and PC3M, a highly metastatic clone of PC3 that has high expression levels of EpCAM. We demonstrate that CAR-expressing PBLs can kill PC3M tumor cells in vitro and in vivo. Despite the low expression of EpCAM on PC3 cells, CAR-expressing PBLs significantly inhibited tumor growth and prolonged mouse survival in a PC3 metastasis model, probably by targeting the highly proliferative and metastatic population of cancer cells.Conclusions
Our data demonstrate that PBLs expressing with EpCAM-specific CARs have significant anti-tumor activity against prostate cancer. Therefore, the adoptive transfer of T cells targeting EpCAM could have great potential as a cancer treatment. 相似文献6.
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Zakrzewski JL Holland AM van den Brink MR 《Journal of molecular medicine (Berlin, Germany)》2007,85(8):837-843
Strategies to enhance post-transplant immune reconstitution without aggravating graft-vs-host disease (GVHD) can improve the outcome of allogeneic hematopoietic stem cell transplantation. Recent preclinical studies demonstrated that the use of T cell depleted allografts supplemented with committed progenitor cells (vs stem cells only) allows enhanced immune reconstitution of specific hematopoietic lineages including myeloid, B, T, and natural killer lineages in the absence of GVHD. This novel adoptive therapy resulted in significantly improved resistance to microbial pathogens and could, in some cases, even mediate tumor immunity. Clinical protocols using adoptive transfer of committed hematopoietic progenitor cells are currently being evaluated. 相似文献
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Recent clinical success has underscored the potential for immunotherapy based on the adoptive cell transfer (ACT) of engineered T lymphocytes to mediate dramatic, potent, and durable clinical responses. This success has led to the broader evaluation of engineered T-lymphocyte-based adoptive cell therapy to treat a broad range of malignancies. In this review, we summarize concepts, successes, and challenges for the broader development of this promising field, focusing principally on lessons gleaned from immunological principles and clinical thought. We present ACT in the context of integrating T-cell and tumor biology and the broader systemic immune response. 相似文献
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Adoptive cellular gene therapy of autoimmune disease 总被引:2,自引:0,他引:2
Slavin AJ Tarner IH Nakajima A Urbanek-Ruiz I McBride J Contag CH Fathman CG 《Autoimmunity reviews》2002,1(4):213-219
Autoimmune disorders represent inappropriate immune responses directed at self-tissue. Because CD4+ T cells are important mediators in the pathogenesis of autoimmune disease, they are ideal candidates for cell-based gene therapy. Using retrovirally-transduced cells and luciferase bioluminescence, we have demonstrated that primary T cells and hybridomas, rapidly and preferentially home to the sites of inflammation in organ-specific autoimmune disease. These cells, transduced with retroviral vectors to drive expression of various 'regulatory proteins', such as IL-4, IL-10 and IL-12p40, deliver these immunoregulatory proteins to the inflamed lesions, providing therapy for experimental models of autoimmune disease such as EAE, CIA and NOD mice. This technique was originally developed in our lab in the murine model of multiple sclerosis, EAE, where T cell hybridomas reactive with myelin basic protein (MBP) were transduced to express and used to deliver the modulatory cytokine, IL-4. Recently we have observed that the cytokine receptor antagonist, IL-12p40 transduced anti-myelin basic protein (MBP) TCR-transgenic T cells (but not CII-reactive T cells) were effective in preventing EAE whereas the CII-reactive, but not MBP-reactive T cells, transduced to express IL-12p40, would treat CIA. 相似文献
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Amanda M. Holland Johannes L. Zakrzewski Gabrielle L. Goldberg Arnab Ghosh Marcel R. M. van den Brink 《Seminars in immunopathology》2008,30(4):479-487
Hematopoietic stem cell transplantation is a curative therapy for hematological malignancies. T cell deficiency following
transplantation is a major cause of morbidity and mortality. In this review, we discuss adoptive transfer of committed precursor
cells to enhance T cell reconstitution and improve overall prognosis after transplantation. 相似文献
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Graft-versus-tumor effect is well recognized in allogeneic transplantation, but it appears to be disease specific and relapse remains a significant problem. Furthermore, immune reconstitution after hematopoietic cell transplantation is often delayed and incomplete. It is becoming increasingly clear that the immune system is complex and that cooperation between innate and adaptive immunity is required to induce a productive immune response. Progress in clinically applicable cell separation techniques and knowledge of the signals required for effective immune activation have made adoptive therapy with T cells and NK cells a viable treatment option. However, clinical efficacy with either cell type depends on in vivo expansion of the infused product, which is facilitated through mechanisms that are active after lymphodeletion. Although successes have been seen with several approaches, further study of immune biology, lymphocyte cooperation and the role of regulatory T cells will lead to better strategies to exploit adoptive transfer of lymphocytes for therapeutic benefit. 相似文献
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Comoli P Maccario R Locatelli F Grossi P Baldanti F Revello MG Gerna G 《Herpes : the journal of the IHMF》2000,7(1):9-12
Profound suppression of T-cell immunity observed after transplantation may permit the emergence of life-threatening viral complications. Prevention or treatment of viral infections in immunocompromised patients through the infusion of small numbers of antigen-specific T-cell lines or clones is the most successful example of adoptive immunotherapy in humans. In fact, adoptive transfer of T cells of donor origin has been demonstrated to be able to restore protective immunity towards these infectious agents and to control established disease. This article reviews human trials of adoptive immunotherapy for herpesvirus-related complications, with the aim of defining principles and problems encountered so far to aid the design of future clinical studies. 相似文献
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《Trends in immunology》2023,44(6):397-398
Functional persistence of chimeric antigen receptor (CAR) T cells is required for sustaining an antitumor response. Recently, Jain et al. revealed that disruption of TET2 in CAR T cells resulted in antigen-independent CAR T cell hyperproliferation that enhanced tumor control in mice, highlighting the potential of epigenetic strategies to improve T cell-based cancer immunotherapy. 相似文献