Cellular immunotherapy of cancer.
ABSTRACT Standard therapies for many common cancers remain toxic and are often ineffective. Cellular immunotherapy has the potential to be a highly targeted alternative, with low toxicity to normal tissues but a high capacity to eradicate tumor. In this chapter we describe approaches that generate cellular therapies using active immunization with cells, proteins, peptides, or nucleic acids, as well as efforts that use adoptive transfer of effector cells that directly target antigens on malignant cells. Many of these approaches are proving successful in hematologic malignancy and in melanoma. In this chapter we discuss the advantages and limitations of each and how over the next decade investigators will attempt to broaden their reach, increase their efficacy, and simplify their application.
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ABSTRACT: Metastatic renal cell carcinoma (mRCC), as one of the most immunogenic tumors has been the focus of adoptive cellular immunotherapy (ACI), but the effects of ACI on objective response and survival in patients with mRCC are still controversial. Therefore, a systematic review and meta-analysis was performed to address this issue. A search was conducted in the PubMed database for randomized clinical trials (RCTs) with ACI in mRCC. All included articles in this study were assessed according to the selection criteria and were divided into two groups: ACI versus no ACI. Outcomes were toxicity, objective response, 1-, 3- and 5-year survival. Risk ratio (RR) and 95% confidence intervals (CI) were calculated using a fixed-effects meta-analysis. Heterogeneity was measured by value of I(2) or P. 4 studies (469 patients) were included. Most of ACI-related adverse reactions were grade 1 or 2 and reversible. ACI provided significant benefit in terms of objective response (RR = 1.65; 95% CI, 1.15 to 2.38; P = 0.007, I(2) = 49%), 1-year survival (RR = 1.30; 95% CI, 1.12 to 1.52; P = 0.0008, I(2) = 0%), 3-year survival (RR = 2.76; 95% CI, 1.85 to 4.14; P<0.00001, I(2) = 46%) and 5-year survival (RR = 2.42; 95% CI, 1.21 to 4.83; P = 0.01, I(2) = 28%). ACI may be a safe and effective treatment for improving objective response, 1-, 3- and 5-year survival in patients with mRCC. Besides, five obstacles for ACI, including high degree of personalization, unsuitable WHO/RECIST response criteria, inadequate identification of tumor-associated antigens (TAAs), lack of effective combination treatments and less attention paid to the quality of ACI products, should be overcome during the successful development of more potent ACI for cancer in the future.PLoS ONE 05/2013; 8(5):e62847. DOI:10.1371/journal.pone.0062847 · 3.53 Impact Factor
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ABSTRACT: Improved outcomes for children with cancer hinge on the development of new targeted therapies with acceptable short-term and long-term toxicity. Progress in basic, preclinical, and clinical arenas spanning cellular immunology, gene therapy, and cell-processing technologies have paved the way for clinical applications of chimeric antigen receptor-based therapies. This is a new form of targeted immunotherapy that merges the exquisite targeting specificity of monoclonal antibodies with the potent cytotoxicity, potential for expansion, and long-term persistence provided by cytotoxic T cells. Although this field is still in its infancy, clinical trials have already shown clinically significant antitumor activity in neuroblastoma, chronic lymphocytic leukemia, and B-cell lymphoma, and trials targeting a variety of other adult and pediatric malignancies are under way. Ongoing work is focused on identifying optimal tumor targets and elucidating and manipulating both cell- and host-associated factors to support expansion and persistence of the genetically engineered cells in vivo. In pediatric oncology, CD19 and GD2 are compelling antigens that have already been identified for targeting pre-B acute lymphoblastic leukemia and neuroblastoma, respectively, with this approach, but it is likely that other antigens expressed in a variety of childhood cancers will also soon be targeted using this therapy. The potential to target essentially any tumor-associated cell-surface antigen for which a monoclonal antibody can be made opens up an entirely new arena for targeted therapy of childhood cancer.Clinical Cancer Research 05/2012; 18(10):2780-90. DOI:10.1158/1078-0432.CCR-11-1920 · 8.19 Impact Factor
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ABSTRACT: Introduction. – Natural killer cells are cytotoxic lymphocytes of innate immunity. These last ten years our knowledge about the mechanisms that regulates NK cell function has greatly improved. Our purpose is to present a review of these new acquisitions and their potential implications in human disease.Current knowledge and key points. – NK cell function is regulated by a repertoire of NK cell receptors and is diversified by recognition of MHC class I by a multigenic and mutiallelic family of NK receptors. Analysis of NK cell repertoire has been used to investigate features that characterize NK cells in pathological situations. Apart from their direct cytotoxic potential to eliminate target cells, recently identification of mechanisms that control NK cell mediated cytokine production and cross talk with dendritic cells emphasize the role of NK cells in the regulation of acquired immune response.Future prospects and projects. – These findings have lead to a better knowledge of the importance of the NK cells in several human diseases. It has been shown that NK cells are actors of the immunosurveillance of tumoral and infectious challenges. Allo or auto reactivity of the NK cell compartment have also been suggested in autoimmune diseases, infertility or foetal loss and transplantation. Ongoing research on NK cells in the fields of human diseases is increasing and will clarify the utility of the evaluation of the NK cell compartment and their receptors in clinical practice.La Revue de Médecine Interne 06/2006; 27(6):465-472. DOI:10.1016/j.revmed.2005.10.022 · 1.32 Impact Factor