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11d
P53-armed Oncolytic Adenovirus Enhances the Efficacy of PD-1 Blockade in Neuroblastoma by Inducing Immunogenic Cell Death. (PubMed, Anticancer Res)
OBP-702 is a promising antitumor strategy to promote the antitumor effect of ICIs by inducing ICD against NB tumors.
Journal • PD(L)-1 Biomarker • IO biomarker
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MYCN (MYCN Proto-Oncogene BHLH Transcription Factor) • HMGB1 (High Mobility Group Box 1)
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PD-L1 expression • MYCN amplification
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Telomelysin (suratadenoturev) • pfifteloxin (OBP-702)
2ms
Turning pancreatic cancer from cold to hot: the promise of a p53-expressing oncolytic adenovirus (OBP-702). (PubMed, Int J Clin Oncol)
Of these agents, Telomelysin (OBP-301, Suratadenoturev), a telomerase-specific oncolytic adenovirus, demonstrated clinical safety but limited efficacy in refractory tumors. Given its multifaceted antitumor functions and ability to overcome key barriers in pancreatic cancer, OBP-702 represents a highly promising therapeutic candidate. A first-in-human clinical trial evaluating endoscopic ultrasonography-guided intratumoral injection of OBP-702 is currently in preparation, expected to advance clinical translation of this novel virotherapeutic strategy.
Review • Journal • Tumor mutational burden • IO biomarker • First-in-human
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KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • CDKN1A (Cyclin-dependent kinase inhibitor 1A) • E2F1 (E2F transcription factor 1)
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TMB-L
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Telomelysin (suratadenoturev) • pfifteloxin (OBP-702)
2ms
Strategically engineering an oncolytic herpes simplex virus to improve systemic delivery. (PubMed, Mol Ther Oncol)
Despite the recent regulatory approvals of oncolytic viruses such as T-VEC (JS1/34.5-/47-/GM-CSF), Oncorine (H101), and Teserpaturev (G47Δ), the clinical impact of OV remains limited by its reliance on intratumoral administration. Preclinical studies demonstrate that FusOn-SD efficiently reaches tumor sites following systemic administration, exhibiting enhanced immune evasion and oncolytic potency. These findings position FusOn-SD as a promising candidate for advancing OV beyond localized injections, with the potential to transform virotherapy into a viable treatment for metastatic cancer.
Journal
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CSF2 (Colony stimulating factor 2)
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Imlygic (talimogene laherparepvec) • Delytact (teserpaturev) • Oncorine (recombinant human adenovirus type 5)
2ms
H101 Plus TACE for r/m HNSCC (clinicaltrials.gov)
P2, N=20, Not yet recruiting, West China Hospital
New P2 trial
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Oncorine (recombinant human adenovirus type 5)
2ms
Innovative Drug and Prodrug Candidates in Cancer Treatment Targeting TP53 Mutations: Challenge and Hope. (PubMed, Drug Dev Res)
Small-molecule correctors, statins, Hsp90 inhibitors, and new drugs like Eprenetapopt and COTI-2 are among the therapeutic options proposed. Challenges such as medication resistance, side effects, and the chemical complexity of p53 pathways are also addressed, emphasizing the importance of ongoing research. This review contributes to our understanding of TP53-targeted cancer medicines, offering hope for more innovative treatments with improved outcomes.
Review • Journal
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TP53 (Tumor protein P53)
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TP53 mutation • TP53 wild-type
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eprenetapopt (APR-246) • COTI-2
2ms
Vaccine Therapy and Pembrolizumab in Treating Patients With Solid Tumors That Have Failed Prior Therapy (clinicaltrials.gov)
P1, N=11, Active, not recruiting, City of Hope Medical Center | Trial completion date: Oct 2025 --> Oct 2026
Trial completion date
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TP53 (Tumor protein P53) • MSI (Microsatellite instability)
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TP53 mutation
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Keytruda (pembrolizumab) • p53MVA
3ms
P53-Armed Oncolytic Virotherapy Promotes the Efficacy of PD1 Blockade in Murine Osteosarcoma Tumors. (PubMed, Anticancer Res)
Our results suggest that P53-armed OBP-702 is a promising agent for improving the antitumor effect of PD1 blockade in treating invasive OS.
Preclinical • Journal • PD(L)-1 Biomarker • IO biomarker
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PD-L2 (Programmed Cell Death 1 Ligand 2)
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PD-L1 expression
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Telomelysin (suratadenoturev) • pfifteloxin (OBP-702)
4ms
Gut microbial metabolite butyrate boosts p53-expressing telomerase-specific oncolytic adenovirus efficacy by enhancing infectivity and activating MHC-I/cGAS-STING. (PubMed, Cancer Immunol Immunother)
These findings were supported by in vivo experiments using CT26 subcutaneous, bilateral, and orthotopic tumor models, in which the combination of oral butyrate and intratumoral OBP-702 administration produced synergistic antitumor effects. These results highlight the therapeutic potential of integrating gut microbial metabolites with oncolytic virotherapy as a novel immunotherapeutic strategy for colorectal cancer.
Journal • IO biomarker
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TP53 (Tumor protein P53) • CD8 (cluster of differentiation 8) • CXCL10 (Chemokine (C-X-C motif) ligand 10) • STING (stimulator of interferon response cGAMP interactor 1)
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pfifteloxin (OBP-702)
4ms
Case report: Local and systemic combination therapy: endoscopic injection of an oncolytic virus with PD-1 inhibitor for an elderly patient with advanced gastrointestinal cancer. (PubMed, Front Immunol)
Subsequently, the patient was treated with an innovative regimen consisting of endoscopic intratumoral injections of Oncolytic adenovirus H101 in combination with the PD-1 inhibitor tislelizumab...The patient achieved nearly 4 months of progression-free survival and a substantial improvement in quality of life. This case highlights the potential of combining oncolytic virotherapy with PD-1 inhibition as a promising and novel personalized strategy for treating elderly patients with advanced gastrointestinal cancers who are unsuitable candidates for conventional therapies.
Journal • PD(L)-1 Biomarker • IO biomarker
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CD8 (cluster of differentiation 8) • CD4 (CD4 Molecule) • CA 19-9 (Cancer antigen 19-9)
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Tevimbra (tislelizumab-jsgr) • Oncorine (recombinant human adenovirus type 5)
5ms
New trial
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5-fluorouracil • Tevimbra (tislelizumab-jsgr) • capecitabine • oxaliplatin • Oncorine (recombinant human adenovirus type 5)
7ms
New P2 trial
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Gendicine (rAd-p53 Gene Therapy)
8ms
ABCC1 promotes GSH-dependent iron transport and resistance to Fe(II) and Cu(II) chelators. (PubMed, Biometals)
Cells expressing ABCC1 displayed significant resistance to thiosemicarbazones (Dp44mT, COTI-2, DpC) in both their metal-free and metal-bound forms. Vesicular transport assays further demonstrated that ABCC1 actively transports the Fe-GSH complex, formed under physiological glutathione levels, indicating its role in regulating the labile iron pool and reducing intracellular iron toxicity. These findings underscore the importance of transporter-chelator interactions in shaping drug resistance and sensitivity and highlight the intricate roles of ABC transporters in modulating chelator activity.
Journal
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ABCB1 (ATP Binding Cassette Subfamily B Member 1) • ABCG2 (ATP Binding Cassette Subfamily G Member 2) • ABCC1 (ATP Binding Cassette Subfamily C Member 1)
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COTI-2