Abstract:
:Adoptive cellular therapy has evolved into a powerful force in the battle against cancer, holding promise for curative responses in patients with advanced and refractory tumors. Autologous T cells, reprogrammed to target malignant cells via the expression of a chimeric antigen receptor (CAR) represent the frontrunner in this approach. Tremendous clinical regressions have been achieved using CAR-T cells against a variety of cancers both in numerous preclinical studies and in several clinical trials, most notably against acute lymphoblastic leukemia, and resulted in a very recent United States Food and Drug Administration approval of the first CAR-T-cell therapy. In most studies CARs are transferred to conventional αβT cells. Nevertheless, transferring a CAR into different cell types, such as γδT cells, natural killer cells, natural killer T cells, and myeloid cells has yet received relatively little attention, although these cell types possess unique features that may aid in surmounting some of the hurdles CAR-T-cell therapy currently faces. This review focuses on CAR therapy using effectors beyond conventional αβT cells and discusses those strategies against the backdrop of developing a safe, powerful, and durable cancer therapy.
journal_name
Hum Gene Therjournal_title
Human gene therapyauthors
Harrer DC,Dörrie J,Schaft Ndoi
10.1089/hum.2017.236subject
Has Abstractpub_date
2018-05-01 00:00:00pages
547-558issue
5eissn
1043-0342issn
1557-7422journal_volume
29pub_type
杂志文章,评审abstract::We evaluated the ability of a replication-deficient, recombinant adenoviral vector to transfer the bifunctional gene GAL-TEK, which expresses a marking/therapeutic gene product, to naturally occurring cat fibrosarcomas in situ. GAL-TEK contains an in-frame fusion of the bacterial LacZ gene for histochemical marking of...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.1995.6.9-1215
更新日期:1995-09-01 00:00:00
abstract::Mutations in the alpha-chain of lysosomal hexosaminidase (EC 3.2.1.52) underlie two distinct biochemical phenotypes known as variant B and variant B1 of G(M2) gangliosidosis. This paper shows that the transduction of human B1-type fibroblasts (producing catalytically inactive alpha-chains) with a retroviral vector enc...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/104303401750476267
更新日期:2001-09-20 00:00:00
abstract::The transfer of a drug resistance gene into hematopoietic cells is an approach being investigated to overcome the problem of myelosuppression produced by anticancer drugs. Chemotherapeutic agents are often given in combination in order to increase their effectiveness. Consequently, there is an advantage in designing v...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.1998.9.17-2537
更新日期:1998-11-20 00:00:00
abstract::Systemic administration of currently manufactured viral stocks has not so far achieved sufficient circulating titers to allow therapeutic targeting of metastatic disease. This is due to low initial viral titers, immune inactivation, nonspecific adhesion, and loss of particles. One way to exploit the elegant molecular ...
journal_title:Human gene therapy
pub_type: 杂志文章,评审
doi:10.1089/104303402760128504
更新日期:2002-07-20 00:00:00
abstract::The large amounts of recombinant adeno-associated virus (rAAV) vector needed for clinical trials and eventual commercialization require robust, economical, reproducible, and scalable production processes compatible with current good manufacturing practice. rAAV produced using baculovirus and insect cells satisfies the...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2010.250
更新日期:2011-08-01 00:00:00
abstract::Administration of recombinant adenoviral (AdV) vectors to animals can lead to inflammatory and immune responses. For therapeutic indications in which repeated treatment is necessary, such as cystic fibrosis (CF), these responses can limit the therapeutic usefulness of the vector. In principle, the utility of the vecto...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/104303401300042348
更新日期:2001-03-20 00:00:00
abstract::We report a novel method for targeting adenovirus-mediated gene delivery. By irradiating mammalian cells prior to adenoviral transduction, adenoviral gene transfer is greatly improved and the adenoviral genome integrates into cellular DNA. In this work, human and rodent cell lines were irradiated and subsequently tran...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.1997.8.9-1025
更新日期:1997-06-10 00:00:00
abstract::This study focuses on the design, construction, and evaluation of a chimeric promoter for gene therapy applications where it is desirable to have low-level basal expression of the newly transferred gene, which can be induced to higher levels of expression by the administration of pharmacologic agents that can be safel...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.1996.7.15-1883
更新日期:1996-10-01 00:00:00
abstract::The recombinant adenoviral (Ad) vector is being considered as a cancer vaccine platform because it efficiently induces immune responses to tumor antigens by intradermal immunization. The aims of this study were to evaluate the potential toxicities and biodistribution after a single dose or six weekly intradermal doses...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2006.17.705
更新日期:2006-07-01 00:00:00
abstract::Adult T cell leukemia/lymphoma (ATL) is derived from CD4+ T cells and has a poor prognosis because of its resistance to chemotherapy. To evaluate the effectiveness of gene therapy for ATL, the effect of ganciclovir on ATL cell lines transfected with the thymidine kinase gene of herpes simplex virus type 1 (HSV-TK) was...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.1996.7.18-2203
更新日期:1996-12-01 00:00:00
abstract::Clinical gene transfer research has involved adult and child subjects, and it is expected that gene transfer in fetal subjects will occur in the future. Some genetic diseases have serious adverse effects on the fetus before birth, and there is hope that prenatal gene therapy could prevent such disease progression. Res...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2011.062
更新日期:2011-11-01 00:00:00
abstract::Gene transfer of reporter genes may trigger immune responses against the heterologous protein resulting in shortening of gene expression and inflammation. We generated transgenic rats expressing the lacZ gene under the control of the human immunodeficiency virus type 1 (HIV-1) long-terminal repeat (LTR) (HIV-lacZ) to ...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/104303402760128603
更新日期:2002-07-20 00:00:00
abstract::Human serum is known to inactivate many retroviruses, including murine leukemia viruses (MLV). Exposure of vectors based on MLV to human serum components would presumably decrease the efficiency of gene transfer in vivo. Human serum also lyses xenogeneic cells, which would affect the survival of retroviral vector pack...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.1995.6.5-635
更新日期:1995-05-01 00:00:00
abstract::Cell-based therapy for muscular dystrophies was initiated in humans after promising results obtained in murine models. Early trials failed to show substantial clinical benefit, sending researchers back to the bench, which led to the discovery of many hurdles as well as many new venues to optimize this therapeutic stra...
journal_title:Human gene therapy
pub_type: 杂志文章,评审
doi:10.1089/hum.2015.139
更新日期:2016-02-01 00:00:00
abstract::Gene-modified replication-competent adenoviruses (Ads) are emerging as a promising new modality for the treatment of cancer. We have previously shown that E1B 19kDa and E1B 55kDa gene-deleted Ad (Ad-DeltaE1B19/55) exhibits improved tumor-specific replication and cell lysis, leading to an enhanced antitumor effect. In ...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2006.167
更新日期:2007-09-01 00:00:00
abstract::Interleukin-12 (IL-12) is a cytokine that exhibits pleiotropic effects on lymphocytes and natural killer cells and has been shown to have promise for the immunotherapy of cancer. The combination of the immune costimulatory molecule B7.1 and IL-12 has been shown to be synergistic for T cell activation. By transfecting ...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.1997.8.9-1125
更新日期:1997-06-10 00:00:00
abstract::Recombinant adeno-associated virus (AAV)-based vectors expressing therapeutic gene products have shown great potential for human gene therapy. One major challenge for translation of promising research to clinical development is the manufacture of sufficient quantities of AAV vectors that meet stringent standards for p...
journal_title:Human gene therapy
pub_type: 杂志文章,评审
doi:10.1089/hum.2009.064
更新日期:2009-07-01 00:00:00
abstract::Human adenoviruses are the most widely used vectors in gene medicine, with applications ranging from oncolytic therapies to vaccinations, but adenovirus vectors are not without side effects. In addition, natural adenoviruses pose severe risks for immunocompromised people, yet infections are usually mild and self-limit...
journal_title:Human gene therapy
pub_type: 杂志文章,评审
doi:10.1089/hum.2014.001
更新日期:2014-04-01 00:00:00
abstract::Janus kinase 3 (JAK3) is an essential component of cytokine receptor signal transduction pathways required for normal lymphocyte development and function. JAK3 deficiency in both mice and humans results in severe combined immunodeficiency (SCID) and increased susceptibility to opportunistic infections. We have previou...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/104303400750038462
更新日期:2000-11-20 00:00:00
abstract::Williams-Beuren syndrome (WBS) and supravalvular aortic stenosis (SVAS) are genetic syndromes marked by the propensity to develop severe vascular stenoses. Vascular lesions in both syndromes are caused by haploinsufficiency of the elastin gene. We used these distinct genetic syndromes as models to evaluate the feasibi...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2011.201
更新日期:2012-11-01 00:00:00
abstract::Serum-induced inactivation of retroviruses is the most critical limitation for in vivo gene transfer therapy. To solve this problem, we searched for reagents that protect retroviruses from inactivation. The effects of the protease inhibitors FOY-007 and FOY-305 and of an inhibitor of the complement pathway FUT-175, al...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.1997.8.13-1575
更新日期:1997-09-01 00:00:00
abstract::An alternative form of gene therapy involves immunoisolation of a nonautologous cell line engineered to secrete a therapeutic product. Encapsulation of these cells in a biocompatible polymer serves to protect these allogeneic cells from host-versus-graft rejection while recombinant products and nutrients are able to p...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2004.15.945
更新日期:2004-10-01 00:00:00
abstract::Silencing of Wnt antagonists with aberrant activation of Wnt signaling is a common phenomenon in various human cancers. Wnt inhibitory factor-1 (WIF-1) is a secreted antagonist of Wnt signaling and acts through direct binding to Wnt in the extracellular space. In this study, we tried to illuminate the impact of WIF-1 ...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2006.005
更新日期:2007-04-01 00:00:00
abstract::Huntington's disease (HD) is a fatal neurodegenerative disease caused by a genetic expansion of the CAG repeat region in the huntingtin (HTT) gene. Studies in HD mouse models have shown that artificial miRNAs can reduce mutant HTT, but evidence for their effectiveness and safety in larger animals is lacking. HD transg...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2017.199
更新日期:2018-06-01 00:00:00
abstract::Isolated methylmalonic acidemia (MMA), a group of autosomal recessive inborn errors of metabolism, is most commonly caused by complete (mut(0)) or partial (mut(-)) deficiency of the enzyme methylmalonyl-CoA mutase (MUT). The severe metabolic instability and increased mortality experienced by many affected individuals,...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2015.092
更新日期:2016-05-01 00:00:00
abstract::Current clinical gene therapy protocols for the treatment of human immunodeficiency virus type 1 (HIV-1) infection often involve the ex vivo transduction and expansion of CD4+ T cells derived from HIV-positive patients at a late stage in their disease (CD4 count <400). These protocols involve the transduction of T cel...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.1998.9.4-487
更新日期:1998-03-01 00:00:00
abstract::With the aim of developing new gene transfer tools for treating CF with gene therapy, we have synthesized a novel family of molecules named cationic phosphonolipids. The most efficient among them were selected by in vitro screening to compare their activities in vivo in mouse lungs. We used a reporter gene whose activ...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.1998.9.16-2309
更新日期:1998-11-01 00:00:00
abstract::Airway infiltration by eosinophils is a major characteristic of chronic asthma. CCL11 (eotaxin-1) is secreted by lung epithelial cells and functions as the major chemokine for eosinophil recruitment. Pseudotyped adeno-associated virus (AAV) 2/9, composed by the AAV2 rep and AAV9 cap genes, can efficiently target lung ...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2012.012
更新日期:2012-11-01 00:00:00
abstract::In summary, I will reiterate the five points I would like to leave with you today: First, the biological revolution has extraordinary power to do good. As long as the use of our new genetic knowledge is guided by the traditional ideals of the healing professions--to help improve the human condition without doing harm-...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.1992.3.1-51
更新日期:1992-02-01 00:00:00
abstract::Hemophilia arthropathy (HA) represents the majority of morbidity in severe hemophilia patients, especially in resource-limited countries. Adeno-associated virus (AAV)-mediated gene therapy is showing promise for managing hemophilia. However, patients with neutralizing antibodies (NAbs) against AAV, and inhibitors to c...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2019.355
更新日期:2020-04-01 00:00:00