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Concurrent OX40 and...
Concurrent OX40 and CD30 Ligand Blockade Abrogates the CD4-Driven Autoimmunity Associated with CTLA4 and PD1 Blockade while Preserving Excellent Anti-CD8 Tumor Immunity
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- Nawaf, Maher G. (författare)
- Univ Birmingham, Inst Immunol & Immunotherapy, Birmingham B15 2TT, W Midlands, England.;Univ Birmingham, Inst Biomed Res, Coll Med & Dent Sci, Birmingham B15 2TT, W Midlands, England.
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- Ulvmar, Maria H. (författare)
- Uppsala universitet,Vaskulärbiologi
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- Withers, David R. (författare)
- Univ Birmingham, Inst Immunol & Immunotherapy, Birmingham B15 2TT, W Midlands, England.;Univ Birmingham, Inst Biomed Res, Coll Med & Dent Sci, Birmingham B15 2TT, W Midlands, England.
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- McConnell, Fiona M. (författare)
- Univ Birmingham, Inst Immunol & Immunotherapy, Birmingham B15 2TT, W Midlands, England.;Univ Birmingham, Inst Biomed Res, Coll Med & Dent Sci, Birmingham B15 2TT, W Midlands, England.
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- Gaspal, Fabrina M. (författare)
- Univ Birmingham, Inst Immunol & Immunotherapy, Birmingham B15 2TT, W Midlands, England.;Univ Birmingham, Inst Biomed Res, Coll Med & Dent Sci, Birmingham B15 2TT, W Midlands, England.
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- Webb, Gwilym J. (författare)
- Univ Birmingham, Inst Immunol & Immunotherapy, Birmingham B15 2TT, W Midlands, England.;Univ Birmingham, Inst Biomed Res, Coll Med & Dent Sci, Birmingham B15 2TT, W Midlands, England.
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- Jones, Nick D. (författare)
- Univ Birmingham, Inst Immunol & Immunotherapy, Birmingham B15 2TT, W Midlands, England.;Univ Birmingham, Inst Biomed Res, Coll Med & Dent Sci, Birmingham B15 2TT, W Midlands, England.
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- Yagita, Hideo (författare)
- Univ Birmingham, Inst Immunol & Immunotherapy, Birmingham B15 2TT, W Midlands, England.;Juntendo Univ, Sch Med, Dept Immunol, Tokyo 1138421, Japan.
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- Allison, James P. (författare)
- Univ Texas MD Anderson Canc Ctr, Dept Immunol, Houston, TX 77030 USA.
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- Lane, Peter J. L. (författare)
- Univ Birmingham, Inst Immunol & Immunotherapy, Birmingham B15 2TT, W Midlands, England.;Univ Birmingham, Inst Biomed Res, Coll Med & Dent Sci, Birmingham B15 2TT, W Midlands, England.
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Univ Birmingham, Inst Immunol & Immunotherapy, Birmingham B15 2TT, W Midlands, England;Univ Birmingham, Inst Biomed Res, Coll Med & Dent Sci, Birmingham B15 2TT, W Midlands, England. Vaskulärbiologi (creator_code:org_t)
- 2017-08-01
- 2017
- Engelska.
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Ingår i: Journal of Immunology. - : The American Association of Immunologists. - 0022-1767 .- 1550-6606. ; 199:3, s. 974-981
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https://doi.org/10.4...
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Abstract
Ämnesord
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- Although strategies that block FOXP3-dependent regulatory T cell function (CTLA4 blockade) and the inhibitory receptor PD1 have shown great promise in promoting antitumor immune responses in humans, their widespread implementation for cancer immunotherapy has been hampered by significant off-target autoimmune side effects that can be lethal. Our work has shown that absence of OX40 and CD30 costimulatory signals prevents CD4 T cell-driven autoimmunity in Foxp3-deficient mice, suggesting a novel way to block these side effects. In this study, we show that excellent antitumor CD8 T cell responses can be achieved in Foxp3(KO) mice deficient in OX40 and CD30 signals, particularly in the presence of concurrent PD1 blockade. Furthermore, excellent antitumor immune responses can also be achieved using combinations of Abs that block CTLA4, PD1, OX40, and CD30 ligands, without CD4 T cell-driven autoimmunity. By dissociating autoimmune side effects from anticancer immune responses, this potentially shifts this antitumor approach to patients with far less advanced disease.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Immunologi inom det medicinska området (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Immunology in the medical area (hsv//eng)
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Nawaf, Maher G.
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Ulvmar, Maria H.
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Withers, David R ...
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McConnell, Fiona ...
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Gaspal, Fabrina ...
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Webb, Gwilym J.
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visa fler...
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Jones, Nick D.
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Yagita, Hideo
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Allison, James P ...
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Lane, Peter J. L ...
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Uppsala universitet