Target Information

Target General Infomation
Target ID
T14755
Former ID
TTDR00284
Target Name
Tumor necrosis factor ligand superfamily member 5
Gene Name
CD40LG
Synonyms
CD154 antigen; CD40 ligand; CD40-L; CD40L; T cell antigen Gp39; TNF-related activation protein; TRAP; CD40LG
Target Type
Clinical Trial
Disease Autoimmune diabetes [ICD10: E08-E13]
B-cell lymphoma [ICD9: 202.8; ICD10: C85.1]
Chronic lymphocytic leukaemia; Mantle cell lymphoma; Small lymphocytic lymphoma [ICD9:200.0, 200.4, 202.0, 202.8, 204.0, 204.1V10.60, 208.9; ICD10: C91, C81-C86, C82, C83.3, C85.7, C91-C95, C91.0, C91.1]
Cancer [ICD9: 140-229; ICD10: C00-C96]
Chronic lymphocytic leukaemia [ICD10: C91]
Lymphoma [ICD9: 202.8, 208.9; ICD10: C81-C86]
Large B-cell lymphoma; Non-hodgkin's lymphoma [ICD9: 202.8; ICD10: C81-C86]
Melanoma [ICD9: 172; ICD10: C43]
Prostate cancer [ICD9: 185; ICD10: C61]
Rheumatoid arthritis [ICD9: 710-719, 714; ICD10: M05-M06]
Sjogren's syndrome [ICD9: 710.2; ICD10: M35.0]
Systemic lupus erythematosus [ICD9: 710; ICD10: M32]
Thrombocytopenia [ICD9: 287.3, 287.4, 287.5; ICD10: D69.6, P61.0]
Function
Release of soluble CD40L from platelets is partially regulated by GP IIb/IIIa, actin polymerization, and an matrix metalloproteinases (MMP) inhibitor-sensitive pathway.
BioChemical Class
Cytokine: tumor necrosis factor
UniProt ID
P29965
Sequence
MIETYNQTSPRSAATGLPISMKIFMYLLTVFLITQMIGSALFAVYLHRRLDKIEDERNLH
EDFVFMKTIQRCNTGERSLSLLNCEEIKSQFEGFVKDIMLNKEETKKENSFEMQKGDQNP
QIAAHVISEASSKTTSVLQWAEKGYYTMSNNLVTLENGKQLTVKRQGLYYIYAQVTFCSN
REASSQAPFIASLCLKSPGRFERILLRAANTHSSAKPCGQQSIHLGGVFELQPGASVFVN
VTDPSQVSHGTGFTSFGLLKL
Drugs and Mode of Action
Drug(s) IL-2/CD40L-expressing leukemia vaccine Drug Info Phase 2 Chronic lymphocytic leukaemia [523912]
ISF35 Drug Info Phase 2 Chronic lymphocytic leukaemia; Mantle cell lymphoma; Small lymphocytic lymphoma [522732]
Lucatumumab Drug Info Phase 2 Lymphoma [521739]
PG-102 Drug Info Phase 2 Autoimmune diabetes [523012]
BI 655064 Drug Info Phase 1 Rheumatoid arthritis [524565]
BPX-101 Drug Info Phase 1 Prostate cancer [522616]
CDP-7657 Drug Info Phase 1 Systemic lupus erythematosus [522990]
Chi Lob 7/4 Drug Info Phase 1 B-cell lymphoma [523848]
CP-870893 Drug Info Phase 1 Cancer [523006]
MEDI4920 Drug Info Phase 1 Sjogren's syndrome [524779]
UltraCD40L Drug Info Phase 1 Systemic lupus erythematosus [544212]
IDEC-131 Drug Info Discontinued in Phase 1 Thrombocytopenia [546380]
Antova Drug Info Terminated Thrombocytopenia [546796]
Dacetuzumab Drug Info Terminated Large B-cell lymphoma; Non-hodgkin's lymphoma [537129]
Modulator Antova Drug Info
Chi Lob 7/4 Drug Info
Dacetuzumab Drug Info
Lucatumumab Drug Info
PG-102 Drug Info
UltraCD40L Drug Info [544292]
Binder ISF35 Drug Info [533021]
Inhibitor MEDI4920 Drug Info [524779], [531635]
Target Expression Profile (TEP) and Drug Resistance Mutation (DRM)
TEP EXP Info
Pathways
KEGG Pathway Cytokine-cytokine receptor interaction
NF-kappa B signaling pathway
Cell adhesion molecules (CAMs)
T cell receptor signaling pathway
Intestinal immune network for IgA production
Malaria
Toxoplasmosis
Asthma
Autoimmune thyroid disease
Systemic lupus erythematosus
Allograft rejection
Primary immunodeficiency
Viral myocarditis
NetPath Pathway IL2 Signaling Pathway
TNFalpha Signaling Pathway
TCR Signaling Pathway
Pathway Interaction Database IL4-mediated signaling events
CD40/CD40L signaling
Calcineurin-regulated NFAT-dependent transcription in lymphocytes
Beta2 integrin cell surface interactions
Calcium signaling in the CD4+ TCR pathway
Reactome Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell
TNFR2 non-canonical NF-kB pathway
TNF receptor superfamily (TNFSF) members mediating non-canonical NF-kB pathway
WikiPathways Inflammatory Response Pathway
Allograft Rejection
Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell
References
Ref 521739ClinicalTrials.gov (NCT00231166) Safety, Efficacy, Dose-finding Study of a Monoclonal Antibody in Patients With Multiple Myeloma. U.S. National Institutes of Health.
Ref 522616ClinicalTrials.gov (NCT00868595) MTD Study of Vaccine BP-GMAX-CD1 Plus AP1903 to Treat Castrate Resistant Prostate Cancer. U.S. National Institutes of Health.
Ref 522732ClinicalTrials.gov (NCT00942409) Study of Repeat Intranodal Injection of Memgen's Cancer Vaccine, Ad-ISF35, in Subjects With Non-Hodgkin's Lymphoma (Follicular, Diffuse Large Cell, Mantle Cell, and Small Lymphocytic Lymphoma/Chronic Lymphocytic Leukemia. U.S. National Institutes of Health.
Ref 522990ClinicalTrials.gov (NCT01093911) Safety Study of CDP7657 in Healthy Volunteers and Patients With Systemic Lupus Erythematosus (SLE). U.S. National Institutes of Health.
Ref 523006ClinicalTrials.gov (NCT01103635) Tremelimumab and CP-870,893 in Patients With Metastatic Melanoma. U.S. National Institutes of Health.
Ref 523012ClinicalTrials.gov (NCT01106703) The Effects of PG102, a Water Soluble Extract From Actinidia Arguta, on Serum Total IgE Levels. U.S. National Institutes of Health.
Ref 523848ClinicalTrials.gov (NCT01561911) A Phase I Study of the Chimeric Anti-CD40 Monoclonal Antibody ChiLob 7/4 to Treat Advanced Malignancies Refractory to Conventional Anti-cancer Treatment. U.S. National Institutes of Health.
Ref 523912ClinicalTrials.gov (NCT01604031) Treatment of B-CLL With Autologous IL2 and CD40 Ligand-Expressing Tumor Cells + Lenalidomide. U.S. National Institutes of Health.
Ref 524565ClinicalTrials.gov (NCT02009761) Multiple Rising Does Study (Subcutaneous Doses) of BI 655064 in Male and Female Patients With Chronic Primary Immune Thrombocytopenic Purpura (ITP).. U.S. National Institutes of Health.
Ref 524779ClinicalTrials.gov (NCT02151110) A Phase 1, Randomized, Blinded, Placebo-controlled, Single-ascending Dose Study to Evaluate the Safety and Tolerability of MEDI4920 in Healthy Adults. U.S. National Institutes of Health.
Ref 537129New developments in immunosuppressive therapy for heart transplantation. Expert Opin Emerg Drugs. 2009 Mar;14(1):1-21.
Ref 544212Soluble multi-trimeric TNF superfamily ligand adjuvants enhance immune responses to a HIV-1 Gag DNA vaccine. Vaccine. 2012 January 17; 30(4): 691-702.
Ref 546380Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800007783)
Ref 546796Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800010330)
Ref 524779ClinicalTrials.gov (NCT02151110) A Phase 1, Randomized, Blinded, Placebo-controlled, Single-ascending Dose Study to Evaluate the Safety and Tolerability of MEDI4920 in Healthy Adults. U.S. National Institutes of Health.
Ref 525972Phase I clinical trial of a monoclonal antibody against CD40-ligand (IDEC-131) in patients with systemic lupus erythematosus. J Rheumatol. 2001 Jan;28(1):95-101.
Ref 527821Immunotherapy of high-risk acute leukemia with a recipient (autologous) vaccine expressing transgenic human CD40L and IL-2 after chemotherapy and allogeneic stem cell transplantation. Blood. 2006 Feb15;107(4):1332-41. Epub 2005 Oct 25.
Ref 531635Therapeutic target database update 2012: a resource for facilitating target-oriented drug discovery. Nucleic Acids Res. 2012 Jan;40(Database issue):D1128-36.
Ref 532263Phase I study of the CD40 agonist antibody CP-870,893 combined with carboplatin and paclitaxel in patients with advanced solid tumors. Oncoimmunology. 2013 Jan 1;2(1):e23033.
Ref 532273Characterization of CD8+ T-cell responses in the peripheral blood and skin injection sites of melanoma patients treated with mRNA electroporated autologous dendritic cells (TriMixDC-MEL). Biomed Res Int. 2013;2013:976383.
Ref 532466A phase I study of an agonist CD40 monoclonal antibody (CP-870,893) in combination with gemcitabine in patients with advanced pancreatic ductal adenocarcinoma. Clin Cancer Res. 2013 Nov 15;19(22):6286-95.
Ref 533021Intratumoral injection of Ad-ISF35 (Chimeric CD154) breaks tolerance and induces lymphoma tumor regression. Hum Gene Ther. 2015 Jan;26(1):14-25.
Ref 533182First-in-human trial of the safety, pharmacokinetics and immunogenicity of a PEGylated anti-CD40L antibody fragment (CDP7657) in healthy individuals and patients with systemic lupus erythematosus. Lupus. 2015 Sep;24(10):1045-56.
Ref 533313CDP7657, an anti-CD40L antibody lacking an Fc domain, inhibits CD40L-dependent immune responses without thrombotic complications: an in vivo study. Arthritis Res Ther. 2015 Sep 3;17:234.
Ref 544241Activation of antigen-exposed iMC-DCs at the ??ight place??and ??ight time??promotes potent anti-tumor immunity. Oncoimmunology. 2012 May 1; 1(3): 362-363.
Ref 544292CD40L-Tri, a novel formulation of recombinant human CD40L that effectively activates B cells. Cancer Immunol Immunother. 2013 February; 62(2): 347-357.
Ref 549729FRI0167 Patient-Reported Outcomes (PROS) During Treatment with Mavrilimumab, A Fully Human Monoclonal Antibody Targeting GM-CSFR-Alpha, In the Phase IIB Earth Explorer 1 Study

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