Basic Information

Gene symbol CD40LG Synonyms CD154, CD40L, HIGM1, IGM, IMD3, T-BAM, TNFSF5, TRAP, gp39, hCD40L Type of gene protein-coding
Gene perturbation-related omics dataset PerturbAtlas | PertOrg
Description CD40 ligand

Gene symbol E2F1 Synonyms E2F-1, RBAP1, RBBP3, RBP3 Type of gene protein-coding
Gene perturbation-related omics dataset PerturbAtlas | PertOrg
Description E2F transcription factor 1

Gene symbol TNFSF9 Synonyms 4-1BB-L, CD137L, TNLG5A Type of gene protein-coding
Description TNF superfamily member 9

GTO ID GTC3986
Trial ID NCT02705196
Disease Pancreatic Cancer
Altered gene E2F1|CD40LG|TNFSF9
Therapeutic/Target gene Therapeutic gene
TherapyDNA oncolytic virus
Treatment LOAd703|delolimogene mupadenorepvec
Co-treatment gemcitabine|nab-paclitaxel
PhasePhase1|Phase2
Recruitment statusRecruiting
TitlePhase I/IIa Trial Evaluating Safety of LOAd703, an Armed Oncolytic Adenovirus for Pancreatic Cancer
Year2016
CountryUnited States
Company sponsorLokon Pharma AB
Other ID(s)LOKON001
Vector information
Vectoradenovirus
ConstructAd5/35-E2F-delta24
Vector typenovel oncolytic serotype 5/35 adenovirus
Transgene/Inserted geneCD40L, which includes CD40-mediated tumor cell apoptosis and adaptive immune activation; and 4-1BBL, which enhances immunologic memory and expands natural killer (NK) cells.
Regulatory elementa cytomegalovirus (CMV) promoter
Viral genome modificationThe gene sequence of trimerized membrane-bound (TMZ)-CD40L, alone or in combination with 4-1BBL (LOAd703), separated by a T2A peptide, was synthesized with a cytomegalovirus (CMV) promoter upstream of the 5′ gene and adenovirus-flanking regions for homologous recombination into adenoviral vectors at both ends.
Vector production methodViruses were produced by transfection of 293 cells (ATCC), followed by expansion in A549 cells (ATCC). The virus supernatants were purified by CsCl gradient centrifugation and diluted in 20 mmol/L Tris, 25 mmol/L NaCl, and 2.5% glycerol. The viable virus titer was measured using a fluorescence-forming units (ffu) assay. The LOAd(−) is the basic LOAd virus without the CMV transgene cassette.
Additional featureCD40L|4-1BBL

Clinical Result

Cohort1: dose level 1
Administration route intratumoral injection|intravenous infusion
Dosage LOAd703, 5E10 viral particles per treatment|gemcitabine, 1000mg/m2|nab-paclitaxel, 125 mg/m2
Age Adult, Older_Adult
References PMID: 38547893
Cohort2: dose level 2
Administration route intratumoral injection|intravenous infusion
Dosage LOAd703, 1E11 viral particles per treatment|gemcitabine, 1000mg/m2|nab-paclitaxel, 125 mg/m2
Age Adult, Older_Adult
References PMID: 38547893
Cohort3: dose level 3
Administration route intratumoral injection|intravenous infusion
Dosage LOAd703, 5E11 viral particles per treatment|gemcitabine, 1000mg/m2|nab-paclitaxel, 125 mg/m2
Age Adult, Older_Adult
References PMID: 38547893
Cohort4: dose level 2_atezolizumab
Administration route intratumoral injection|intravenous infusion
Dosage LOAd703, 1E11 viral particles per treatment|gemcitabine, 1000mg/m2|nab-paclitaxel, 125 mg/m2
Age Adult, Older_Adult
References PMID: 38547893
Cohort5: dose level 2_atezolizumab
Administration route intratumoral injection|intravenous infusion
Dosage LOAd703, E11 viral particles per treatment|gemcitabine, 1000mg/m2|nab-paclitaxel, 125 mg/m2
Age Adult, Older_Adult
References PMID: 38547893

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