Abstract：
:Recombinant immunotoxins (RITs) are chimeric proteins designed to treat cancer. They are made up of an Fv or Fab that targets an antigen on a cancer cell fused to a 38-kDa portion of Pseudomonas exotoxin A (PE38). Because PE38 is a bacterial protein, it is highly immunogenic in patients with solid tumors that have normal immune systems, but much less immunogenic in patients with hematologic malignancies where the immune system is suppressed. RITs have shown efficacy in refractory hairy cell leukemia and in some children with acute lymphoblastic leukemia, but have been much less effective in solid tumors, because neutralizing antibodies develop and prevent additional treatment cycles. In this paper we will (i) review data from clinical trials describing the immunogenicity of PE38 in different patient populations; (ii) review results from clinical trials using different immunosuppressive drugs; and (iii) describe our efforts to make new less-immunogenic RITs by identifying and removing T- and B-cell epitopes to hide the RIT from the immune system.
journal_name
Immunol Revjournal_title
Immunological reviewsauthors
Mazor R,Onda M,Pastan Idoi
10.1111/imr.12390subject
Has Abstractpub_date
2016-03-01 00:00:00pages
152-64issue
1eissn
0105-2896issn
1600-065Xjournal_volume
270pub_type
杂志文章,评审abstract：:Directed cellular migrations underlie immune system organization. Chemokines and their receptors (along with surface-adhesion molecules) are central to these migrations, targeting developing and mature leukocytes to tissues and microenvironments suitable for their differentiation and function. The chemokine CXCL12 and...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1034/j.1600-065x.2003.00067.x
更新日期：2003-10-01 00:00:00
abstract：:For more than a century, immunologists and vaccinologists have existed in parallel universes. Immunologists have for long reveled in using 'model antigens', such as chicken egg ovalbumin or nitrophenyl haptens, to study immune responses in model organisms such as mice. Such studies have yielded many seminal insights a...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/imr.12099
更新日期：2013-09-01 00:00:00
abstract：:Fcγ receptors (FcγRs) are key immune receptors responsible for the effective control of both humoral and innate immunity and are central to maintaining the balance between generating appropriate responses to infection and preventing autoimmunity. When this balance is lost, pathology results in increased susceptibility...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/imr.12341
更新日期：2015-11-01 00:00:00
abstract：:Hookworm infection is a major parasitic cause of morbidity in the developing nations of the tropics. Development of a genetically engineered vaccine would be a useful tool in the control of this infection in highly endemic areas. Recombinant polypeptides belonging to the Ancylostoma secreted protein (ASP)-1 family hav...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/j.1600-065x.1999.tb01347.x
更新日期：1999-10-01 00:00:00
abstract：:The general thrust of this volume is to review the roles of accessory cells in regulating T and B lymphocytes. To that end, we have summarized the evidence that indicates the crucial role that Langerhans cells play in the induction and expression of immunity to antigens that gain access to, or arise within, skin. Lang...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/j.1600-065x.1990.tb00572.x
更新日期：1990-10-01 00:00:00
abstract：:Recent advances in two-photon microscopy have provided a new way of visualizing the behavior of fluorescently tagged cells within their natural microenvironment. This technology has allowed for generating a detailed picture of the cellular interaction dynamics operant in the activation of T cells and B cells during pr...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/j.1600-065X.2008.00596.x
更新日期：2008-02-01 00:00:00
abstract：:The endosomal pathway of antigen presentation leads to the display of peptides on major histocompatibility complex (MHC) class II molecules at the cell surface of antigen-presenting cells (APCs). The pathway involves two major steps, invariant chain degradation and antigen processing, which take place in the late endo...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/j.0105-2896.2005.00310.x
更新日期：2005-10-01 00:00:00
abstract：:The current regimens used to treat tuberculosis are largely comprised of serendipitously discovered drugs that are combined based on clinical experience. Despite curing millions, these drug regimens are limited by the long course of therapy, the emergence of resistance, and the persistent tissue damage that remains af...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/imr.12267
更新日期：2015-03-01 00:00:00
abstract：:Mast cells (MCs) are major effector cells of immunoglobulin E (IgE)-mediated allergic inflammation. However, it has become increasingly clear that they also play important roles in diverse physiological and pathological processes. Recent advances have focused on the importance of MCs in both innate and adaptive immune...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/j.0105-2896.2005.00279.x
更新日期：2005-08-01 00:00:00
abstract：:Newfound relatives of the classical Fc receptors (FcR) have been provisionally named the Fc receptor homologs (FcRH). The recent identification of eight human and six mouse FcRH genes substantially increases the size and functional potential of the FcR family. The extended family of FcR and FcRH genes spans approximat...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1034/j.1600-065x.2002.19009.x
更新日期：2002-12-01 00:00:00
abstract：:Over the past two decades, structural biology has shown how T-cell receptors engage peptide/major histocompatibility complex (MHC) complexes and provided insight into the mechanisms underlying antigen specificity and cross-reactivity. Here we review and contextualize our contributions, which have emphasized the influe...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/j.1600-065X.2012.01165.x
更新日期：2012-11-01 00:00:00
abstract：:Over the past 20 years, major progress has been made in our understanding of natural killer (NK) cells. It has become clear that NK cells are regulated by a number of receptors with opposite functions that finely tune potent effector functions such as cytolytic activity and release of cytokines that play a major role ...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/j.1600-065X.2008.00651.x
更新日期：2008-08-01 00:00:00
abstract：:The induction of polyarthritis and polyarthralgia is a hallmark of arthritogenic alphavirus infections, with an exceptionally higher morbidity observed with chikungunya virus (CHIKV). While the mechanisms underlying these incapacitating acute symptoms remain partially understood, the progression to chronic conditions ...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/imr.12825
更新日期：2020-03-01 00:00:00
abstract：:The major histocompatibility complex (MHC) plays a central role in controlling immune responsiveness, susceptibility to certain diseases and histo-incompatibility. A physical map of the complete rat MHC, the RTI complex, is presented based on a PAC clonal contig (RT1n haplotype). Expression profiling of various tissue...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1034/j.1600-065x.2001.1840108.x
更新日期：2001-12-01 00:00:00
abstract：:On the basis of cell surface markers, mature T cells are considered to have either a naïve or a memory phenotype. These cells exhibit distinct types of kinetic behaviour in vivo. While naïve-phenotype cells persist long term in a non-dividing state, memory-phenotype T cells include cycling cells and exhibit a more rap...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/j.1600-065x.1999.tb01327.x
更新日期：1999-08-01 00:00:00
abstract：:There are two distinct pathways by which T cells may recognize MHC alloantigens. The direct pathway involves T-cell recognition of intact MHC molecules expressed by donor antigen-presenting cells (APCs). The second, or indirect, pathway describes T-cell recognition of peptides derived from the processing and presentat...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/j.1600-065x.1998.tb01224.x
更新日期：1998-08-01 00:00:00
abstract：:Hematopoietic stem cells (HSC) have the capacity to reconstitute all the blood cells in the body. HSC are rare, representing on average 0.05% of the mononuclear cells present in healthy human bone marrow. Due to their capacity for self-renewal and their pluripotent, long-term reconstituting potential, HSC are consider...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/j.1600-065x.1997.tb00972.x
更新日期：1997-06-01 00:00:00
abstract：:The sequence analysis of Ig variable region genes transcribed within different B-cell subpopulations from human tonsil led us to identify a rare DNA sequence modification event consisting of bp insertions and/or deletions (I/D). Although these events were previously reported, they had never been formally associated wi...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/j.1600-065x.1998.tb01437.x
更新日期：1998-04-01 00:00:00
abstract：SUMMARY:Interleukin-21 (IL-21) belongs to a family of cytokines that includes IL-2, IL-4, IL-7, IL-9, and IL-15, all of which bind to private (or shared) receptors as well as the common cytokine receptor gamma-chain as a component. Most cytokines in this family are critically important for both the maintenance and func...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/j.1600-065X.2008.00631.x
更新日期：2008-06-01 00:00:00
abstract：:Understanding how the integrins on leukocytes operate is important because these receptors control the activity of leukocytes in all phases of their lives. Thus integrins control leukocyte development and maturation in bone marrow, the circulation of naive cells in secondary lymphoid tissue, e.g. the lymph nodes, and ...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1034/j.1600-065x.2002.18614.x
更新日期：2002-08-01 00:00:00
abstract：:αβ T cells are an integral part of protective immunity against pathogens. After precursor cells arise in the adult bone marrow or fetal liver, they migrate to the thymus where they rearrange their T-cell receptor genes (TCR) and undergo selection on the basis of their interactions with ligands expressed by thymic stro...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/imr.12095
更新日期：2013-09-01 00:00:00
abstract：:Viral infections may induce and sustain autoimmune processes via several and overlapping mechanisms. We outline how chronic inflammation, sustained by persisting viruses, may be "the prerequisite" for initiation and maintenance of the multistep process leading to autoimmunity. Chronic inflammation may favour priming o...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/j.1600-065x.1998.tb01204.x
更新日期：1998-08-01 00:00:00
abstract：:The human leukocyte receptor complex (LRC) contains at least 26 genes which belong to the immunoglobulin superfamily The genes include two clusters of immunoglobulin-like transcript (ILT)/leukocyte immunoglobulin-like receptor (LIR)/monocyte-macrophage inhibitory receptor (MIR) loci, a cluster of killer cell inhibitor...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1034/j.1600-065x.2001.1810103.x
更新日期：2001-06-01 00:00:00
abstract：:The ability of T cells to respond to a wide array of foreign antigens while avoiding reactivity to self is largely determined by cellular selection of developing T cells in the thymus. While a great deal is known about the cell types and molecules involved in T-cell selection in the thymus, our understanding of the sp...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/imr.12398
更新日期：2016-05-01 00:00:00
abstract：:Systems biology is the comprehensive and quantitative analysis of the interactions between all of the components of biological systems over time. Systems biology involves an iterative cycle, in which emerging biological problems drive the development of new technologies and computational tools. These technologies and ...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/j.1600-065X.2008.00721.x
更新日期：2009-01-01 00:00:00
abstract：:Human T cell hybridomas were generated by several techniques and the supernatants generated were screened for activity on human B cells. Three general activities were noted; B cell proliferation factor ( BCPF ), B cell differentiation factor (BCDF), and an IgA isotype-specific helper factor. BCPF acts on B cells to in...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/j.1600-065x.1984.tb00479.x
更新日期：1984-04-01 00:00:00
abstract：:Natural killer cells employ a diverse arsenal of effector mechanisms to target intracellular pathogens. Differentiation of natural killer (NK) cell activation pathways occurs along a continuum from reliance on innate pro-inflammatory cytokines and stress-induced host ligands through to interaction with signals derived...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/imr.12798
更新日期：2020-01-01 00:00:00
abstract：:The infiltration of human tumors by T cells is a common phenomenon, and over the past decades, it has become increasingly clear that the nature of such intratumoral T-cell populations can predict disease course. Furthermore, intratumoral T cells have been utilized therapeutically in clinical studies of adoptive T-cell...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/imr.12140
更新日期：2014-01-01 00:00:00
abstract：:In the century since Paul Portier and Charles Richet described their landmark findings of severe fatal reactions in dogs re-exposed to venom after vaccination with sea anemone venom, treatment for anaphylaxis continues to evolve. The incidence of anaphylaxis continues to be difficult to measure. Underreporting due to ...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/j.1600-065X.2011.01028.x
更新日期：2011-07-01 00:00:00
abstract：:In the quest for effective immunization against complex diseases such as cancer, parasitic diseases, AIDS, and other viral infections, numerous peptides and recombinant proteins have been synthesized, examined for the ability to induce antibodies and CTLs, and tested for binding capability and therapeutic or prophylac...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/j.1600-065x.1995.tb00075.x
更新日期：1995-06-01 00:00:00
