| In vitro co-stimulation with anti-CD28 synergizes with IL-12 in the generation of T cell immune responses to leukaemic cells; a strategy for ex-vivo generation of CTL for immunotherapy. | |
| | |
MedLine Citation:
|
PMID: 12930376 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
The existence of an immune based graft-versus-leukaemia (GvL) effect highlighted the prospect of managing relapsed leukaemias with T cell-based adoptive immunotherapy. Thus, various strategies have been explored for the in vitro expansion of acute myeloid leukaemia (AML)-specific T cells. In a popular approach, AML blasts have been genetically modified to express co-stimulatory molecules essential for effective T cell priming. One such tactic has been the modification of AML cells to express the B7/CD80 co-stimulatory molecule that binds to CD28 on T cells initiating events that culminate in enhanced cytokine production, proliferation and development of effector functions by T cells. The success of these strategies has been limited by difficulties in attaining sufficient transduction efficiencies and associated high levels of CD80 expression. We demonstrate that these problems can be circumvented by using anti-CD28 monoclonal antibody. Furthermore, we show that the synergistic relationship between CD80/CD28 pathway and interleukin 12 cytokine (IL-12), documented in the generation of cytotoxic T lymphocytes (CTL) for solid tumours, also applies to AML. CD28/IL-12 synergy facilitated the proliferation of allogeneic T cells in response to stimulation with primary AML blasts. The synergy also favoured generation of a Th1-type immune response, evidenced by gamma interferon (IFN-gamma) secretion and facilitated naive and memory T cell proliferation. Unlike some methods of in vitro T cell expansion, use of CD28/IL-12 synergy left T cells in the physiologically appropriate CD45RA-/CCR7- subsets known to be associated with immediate cytotoxic functions. |
| | |
Authors:
|
J K Orleans-Lindsay; A Deru; J I O Craig; H G Prentice; M W Lowdell |
Related Documents
:
|
9029026 - Acute lymphoblastic leukaemia in childhood: cell proliferation without rest. 15670816 - Leukaemia inhibitory factor (lif) is functionally linked to axotrophin and both lif and... 2156776 - Lymphocyte subpopulations in sheep with lymphosarcoma resulting from experimental infec... 3864486 - Acute biphenotypic leukaemia (myeloid and null-all type) supervening in a myelodysplast... 17671216 - Human tumor-derived exosomes selectively impair lymphocyte responses to interleukin-2. 2924986 - Increased mast cell numbers in the sclerotic skin of porphyria cutanea tarda. |
Publication Detail:
|
Type: Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
|
Title: Clinical and experimental immunology Volume: 133 ISSN: 0009-9104 ISO Abbreviation: Clin. Exp. Immunol. Publication Date: 2003 Sep |
Date Detail:
|
Created Date: 2003-08-21 Completed Date: 2003-10-14 Revised Date: 2009-11-18 |
Medline Journal Info:
|
Nlm Unique ID: 0057202 Medline TA: Clin Exp Immunol Country: England |
Other Details:
|
Languages: eng Pagination: 467-75 Citation Subset: IM |
Affiliation:
|
Department of Haematology, Royal Free and University College Medical School, London, UK. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Acute Disease Adult Antibodies, Monoclonal / therapeutic use* Antigens, CD28 / immunology* Antigens, CD45 / analysis Antigens, CD80 / immunology Graft vs Leukemia Effect Humans Immunotherapy, Adoptive* Interferon-gamma / secretion Interleukin-12 / immunology* Leukemia, Myeloid / immunology, therapy* Membrane Glycoproteins / metabolism Perforin Pore Forming Cytotoxic Proteins Receptors, CCR7 Receptors, Chemokine / analysis T-Lymphocytes, Cytotoxic / immunology* Th1 Cells / immunology |
| Chemical | |
Reg. No./Substance:
|
0/Antibodies, Monoclonal; 0/Antigens, CD28; 0/Antigens, CD80; 0/CCR7 protein, human; 0/Membrane Glycoproteins; 0/Pore Forming Cytotoxic Proteins; 0/Receptors, CCR7; 0/Receptors, Chemokine; 126465-35-8/Perforin; 187348-17-0/Interleukin-12; 82115-62-6/Interferon-gamma; EC 3.1.3.48/Antigens, CD45 |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: T cell receptor VB repertoire diversity in patients with immune thrombocytopenia following splenecto...
Next Document: Donor dependent, interferon-gamma induced HLA-DR expression on human neutrophils in vivo.