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A novel form of 4-1BBL has better immunomodulatory activity than an agonistic anti-4-1BB Ab without Ab-associated severe toxicity.

Schabowsky RH, Elpek KG, Madireddi S, Sharma RK, Yolcu ES, Bandura-Morgan L, Miller R, MacLeod KJ, Mittler RS, Shirwan H.

Vaccine. 2009 Dec 11;28(2):512-22. doi: 10.1016/j.vaccine.2009.09.127. Epub 2009 Oct 29.


4-1BB ligand as an effective multifunctional immunomodulator and antigen delivery vehicle for the development of therapeutic cancer vaccines.

Sharma RK, Schabowsky RH, Srivastava AK, Elpek KG, Madireddi S, Zhao H, Zhong Z, Miller RW, Macleod KJ, Yolcu ES, Shirwan H.

Cancer Res. 2010 May 15;70(10):3945-54. doi: 10.1158/0008-5472.CAN-09-4480. Epub 2010 Apr 20.


Costimulation as a platform for the development of vaccines: a peptide-based vaccine containing a novel form of 4-1BB ligand eradicates established tumors.

Sharma RK, Elpek KG, Yolcu ES, Schabowsky RH, Zhao H, Bandura-Morgan L, Shirwan H.

Cancer Res. 2009 May 15;69(10):4319-26. doi: 10.1158/0008-5472.CAN-08-3141. Epub 2009 May 12.


A switch in costimulation from CD28 to 4-1BB during primary versus secondary CD8 T cell response to influenza in vivo.

Bertram EM, Dawicki W, Sedgmen B, Bramson JL, Lynch DH, Watts TH.

J Immunol. 2004 Jan 15;172(2):981-8.


The systemic administration of Ig-4-1BB ligand in combination with IL-12 gene transfer eradicates hepatic colon carcinoma.

Xu DP, Sauter BV, Huang TG, Meseck M, Woo SL, Chen SH.

Gene Ther. 2005 Oct;12(20):1526-33.


Adjuvantive effects of anti-4-1BB agonist Ab and 4-1BBL DNA for a HIV-1 Gag DNA vaccine: different effects on cellular and humoral immunity.

Ganguly S, Liu J, Pillai VB, Mittler RS, Amara RR.

Vaccine. 2010 Feb 3;28(5):1300-9. doi: 10.1016/j.vaccine.2009.11.020. Epub 2009 Nov 26.


4-1BB ligand induces cell division, sustains survival, and enhances effector function of CD4 and CD8 T cells with similar efficacy.

Cannons JL, Lau P, Ghumman B, DeBenedette MA, Yagita H, Okumura K, Watts TH.

J Immunol. 2001 Aug 1;167(3):1313-24.


Immune regulation by 4-1BB and 4-1BBL: complexities and challenges.

Wang C, Lin GH, McPherson AJ, Watts TH.

Immunol Rev. 2009 May;229(1):192-215. doi: 10.1111/j.1600-065X.2009.00765.x. Review.


Ex vivo expansion of CD4+CD25+FoxP3+ T regulatory cells based on synergy between IL-2 and 4-1BB signaling.

Elpek KG, Yolcu ES, Franke DD, Lacelle C, Schabowsky RH, Shirwan H.

J Immunol. 2007 Dec 1;179(11):7295-304.


Dispensable role for 4-1BB and 4-1BBL in development of vaccinia virus-specific CD8 T cells.

Zhao Y, Croft M.

Immunol Lett. 2012 Jan 30;141(2):220-6. doi: 10.1016/j.imlet.2011.10.008. Epub 2011 Oct 20.


T-cell intrinsic effects of GITR and 4-1BB during viral infection and cancer immunotherapy.

Snell LM, Lin GH, McPherson AJ, Moraes TJ, Watts TH.

Immunol Rev. 2011 Nov;244(1):197-217. doi: 10.1111/j.1600-065X.2011.01063.x. Review. Erratum in: Immunol Rev. 2012 Jan;245(1):265.


SA-4-1BBL as the immunomodulatory component of a HPV-16 E7 protein based vaccine shows robust therapeutic efficacy in a mouse cervical cancer model.

Sharma RK, Srivastava AK, Yolcu ES, MacLeod KJ, Schabowsky RH, Madireddi S, Shirwan H.

Vaccine. 2010 Aug 16;28(36):5794-802. doi: 10.1016/j.vaccine.2010.06.073. Epub 2010 Jul 4.


SA-4-1BBL costimulation inhibits conversion of conventional CD4+ T cells into CD4+ FoxP3+ T regulatory cells by production of IFN-γ.

Madireddi S, Schabowsky RH, Srivastava AK, Sharma RK, Yolcu ES, Shirwan H.

PLoS One. 2012;7(8):e42459. doi: 10.1371/journal.pone.0042459. Epub 2012 Aug 1. Erratum in: PLoS One. 2012;7(8): doi/10.1371/annotation/88b557df-1e27-4a60-8b47-214a5cc3c707.


In vivo triggering through 4-1BB enables Th-independent priming of CTL in the presence of an intact CD28 costimulatory pathway.

Diehl L, van Mierlo GJ, den Boer AT, van der Voort E, Fransen M, van Bostelen L, Krimpenfort P, Melief CJ, Mittler R, Toes RE, Offringa R.

J Immunol. 2002 Apr 15;168(8):3755-62.


Distinct approaches to investigate the importance of the murine 4-1BB 4-1BBL interaction in the antibody response to Streptococcus pneumoniae.

Moens L, Jeurissen A, Mittler RS, Wuyts G, Michiels G, Boon L, Ceuppens JL, Bossuyt X.

J Leukoc Biol. 2007 Sep;82(3):638-44. Epub 2007 Jun 5.


Combinatorial therapy for liver metastatic colon cancer: dendritic cell vaccine and low-dose agonistic anti-4-1BB antibody co-stimulatory signal.

Lee H, Park HJ, Sohn HJ, Kim JM, Kim SJ.

J Surg Res. 2011 Jul;169(1):e43-50. doi: 10.1016/j.jss.2011.03.067. Epub 2011 Apr 21.


Immunotherapy of cancer with 4-1BB.

Vinay DS, Kwon BS.

Mol Cancer Ther. 2012 May;11(5):1062-70. doi: 10.1158/1535-7163.MCT-11-0677. Epub 2012 Apr 24. Review.


Costimulation of CD28- T lymphocytes by 4-1BB ligand.

DeBenedette MA, Shahinian A, Mak TW, Watts TH.

J Immunol. 1997 Jan 15;158(2):551-9.


Administration of agonistic anti-4-1BB monoclonal antibody leads to the amelioration of experimental autoimmune encephalomyelitis.

Sun Y, Lin X, Chen HM, Wu Q, Subudhi SK, Chen L, Fu YX.

J Immunol. 2002 Feb 1;168(3):1457-65.

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