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DRUG:

pfifteloxin (OBP-702)

i
Other names: OBP-702, OBP 702
Associations
Trials
Company:
Oncolys BioPharma
Drug class:
p53 stimulant
Associations
Trials
9d
Dendritic cell maturation is induced by p53-armed oncolytic adenovirus via tumor-derived exosomes enhancing systemic antitumor immunity. (PubMed, Cancer Immunol Immunother)
We previously developed a telomerase-specific oncolytic adenovirus (OBP-301) and a p53-armed OBP-301 (OBP-702), demonstrating that these viruses strongly activate systemic antitumor immunity. Intratumoral injection of OBP-702 into PAN02 subcutaneous tumors significantly increased the presence of mature DCs and CD8-positive T cells in draining lymph nodes, leading to long-lasting antitumor effects through the durable activation of systemic antitumor immunity. In conclusion, tumor-derived exosomes play a significant role in DC maturation following OBP-702 treatment and are critical for the systemic activation of antitumor immunity, leading to the abscopal effect.
Journal • Oncolytic virus • IO biomarker
|
CD8 (cluster of differentiation 8) • IFNG (Interferon, gamma) • CD80 (CD80 Molecule) • CD86 (CD86 Molecule)
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CD8 positive
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Telomelysin (suratadenoturev) • pfifteloxin (OBP-702)
3ms
p53-armed oncolytic virotherapy induces abscopal effect in osteosarcoma by promoting immunogenic cell death. (PubMed, Mol Ther Oncol)
Here, we show the therapeutic potential of chemotherapeutic drugs (doxorubicin, cisplatin) and telomerase-specific oncolytic adenoviruses (OBP-301, p53-armed OBP-702) to induce ICD in human OS cells (U2OS, MNNG/HOS, SaOS-2) and murine OS cells (NHOS). Subcutaneous NHOS tumor models demonstrated that intratumoral injection of OBP-702 significantly increased the tumor infiltration of cytotoxic CD8+ T cells and induced the abscopal effect against non-treated tumors compared with OBP-301. Our results suggest that OBP-702 is a promising antitumor reagent to induce ICD with secretion of ATP and HMGB1 and the abscopal effect against OS.
Journal • Oncolytic virus
|
CD8 (cluster of differentiation 8) • HMGB1 (High Mobility Group Box 1)
|
cisplatin • doxorubicin hydrochloride • Telomelysin (suratadenoturev) • pfifteloxin (OBP-702)
6ms
Functional remodeling of intraperitoneal macrophages by oncolytic adenovirus restores anti-tumor immunity for peritoneal metastasis of gastric cancer. (PubMed, Mol Ther Oncol)
Furthermore, the combination of intraperitoneal OBP-702 with anti-programmed cell death-1 antibody enhanced anti-tumor immunity and prolonged the survival of mice bearing PM. Intraperitoneal immunotherapy using OBP-702 restores anti-tumor immunity via the remodeling of intraperitoneal macrophages in addition to direct tumor lysis and cooperates with immune checkpoint inhibitors to suppress PM in GC.
Journal • Oncolytic virus • PD(L)-1 Biomarker • IO biomarker
|
CD8 (cluster of differentiation 8) • CD163 (CD163 Molecule)
|
PD-L1 expression • TP53 wild-type
|
pfifteloxin (OBP-702)
7ms
p53-Armed Oncolytic Virotherapy Improves Radiosensitivity in Soft-Tissue Sarcoma by Suppressing BCL-xL Expression. (PubMed, Acta Med Okayama)
We previously demonstrated the therapeutic potential of two telomerase-specific replication-competent oncolytic adenoviruses, OBP-301 and tumor suppressor p53-armed OBP-702, in human STS cells. The in vivo experiments demonstrated that this combination therapy significantly suppressed STS tumors' growth. Our results suggest that OBP-702 is a promising antitumor reagent for promoting the radiosensitivity of STS tumors.
Journal • Oncolytic virus
|
TP53 (Tumor protein P53) • BCL2L1 (BCL2-like 1)
|
Telomelysin (suratadenoturev) • pfifteloxin (OBP-702)
9ms
Long-term activation of anti-tumor immunity in pancreatic cancer by a p53-expressing telomerase-specific oncolytic adenovirus. (PubMed, Br J Cancer)
OBP-702 can be a long-term immunostimulant with sustained anti-tumor effects on immunologically cold pancreatic cancer.
Journal • Oncolytic virus
|
TP53 (Tumor protein P53) • CD8 (cluster of differentiation 8)
|
TP53 expression
|
gemcitabine • albumin-bound paclitaxel • pfifteloxin (OBP-702)
12ms
Therapeutic Effect of Oncolytic Adenovirus on Pancreatic Cancer Stroma (PubMed, Gan To Kagaku Ryoho)
We have developed tumor suppressor gene p53-armed oncolytic adenovirus(OBP-702), and have clarified therapeutic effects on PDAC cells. In this study, we investigate the therapeutic effect of OBP-702 on PDAC CAF.
Journal • Oncolytic virus • Stroma
|
TP53 (Tumor protein P53)
|
pfifteloxin (OBP-702)
12ms
p53-armed oncolytic adenovirus induces autophagy and apoptosis in KRAS and BRAF-mutant colorectal cancer cells. (PubMed, PLoS One)
In BRAF-mutant CRC cells, OBP-301 and OBP-702 suppressed the expression of EGFR, MEK, ERK, and AKT proteins, whereas mTOR expression was suppressed only by OBP-702. Our results suggest that p53-armed oncolytic virotherapy is a viable therapeutic option for treating KRAS/BRAF-mutant CRC cells via induction of autophagy and apoptosis.
Journal • Oncolytic virus
|
EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • DLD (Dihydrolipoamide Dehydrogenase)
|
KRAS mutation • EGFR mutation • BRAF mutation • EGFR expression • KRAS wild-type • BRAF wild-type • RAS wild-type • RAS wild-type + BRAF wild-type
|
Telomelysin (suratadenoturev) • pfifteloxin (OBP-702)
almost2years
Oncolytic virus-mediated reducing of myeloid-derived suppressor cells enhances the efficacy of PD-L1 blockade in gemcitabine-resistant pancreatic cancer. (PubMed, Cancer Immunol Immunother)
Pancreatic ductal adenocarcinoma (PDAC) is often refractory to treatment with gemcitabine (GEM) and immune checkpoint inhibitors including anti-programmed cell death ligand 1 (PD-L1) antibody. Moreover, combination treatment with OBP-702 significantly enhanced the antitumor efficacy of PD-L1 blockade against GEM-resistant PAN02 tumors. The present results suggest that combination therapy involving OBP-702 and PD-L1 blockade is a promising antitumor strategy for treating GEM-resistant PDAC with GM-CSF-induced immunosuppressive TME formation.
Journal • Oncolytic virus • PD(L)-1 Biomarker • IO biomarker
|
TP53 (Tumor protein P53) • CSF2 (Colony stimulating factor 2)
|
PD-L1 expression
|
gemcitabine • pfifteloxin (OBP-702)
2years
Telomerase-Specific Oncolytic Adenovirus Expressing p53 Gene Stimulating CD8+ Memory T Cells in Pancreatic Cancer (PubMed, Gan To Kagaku Ryoho)
We developed telomerase-specific oncolytic adenoviruses (OAs), including OBP-301 that is currently tested in a clinical trial of combined anti-PD-1 antibody and p53-armed OBP- 301 variant(OBP-702). OAs have immune-modulation functions and induce CD8+ T cells into tumors by releasing immunogenic cell death markers, such as extracellular adenosine triphosphate. Here, we investigated the effectiveness of OBP- 702 in pancreatic cancer treatments, focusing on the influence on CD8+ memory T cells.
Journal • Oncolytic virus • PD(L)-1 Biomarker • IO biomarker
|
TP53 (Tumor protein P53) • CD8 (cluster of differentiation 8)
|
TP53 expression
|
Telomelysin (suratadenoturev) • pfifteloxin (OBP-702)
2years
Oncolytic virus-mediated p53 overexpression promotes immunogenic cell death and efficacy of PD-1 blockade in pancreatic cancer. (PubMed, Mol Ther Oncolytics)
Our results suggest that oncolytic adenovirus-mediated p53 overexpression augments ICD and the efficacy of PD-1 blockade therapy against cold PDAC tumors. Further in vivo experiments would be warranted to evaluate the survival benefit of tumor-bearing mice in combination therapy with OBP-702 and PD-1 blockade.
Journal • Oncolytic virus • PD(L)-1 Biomarker • IO biomarker
|
TP53 (Tumor protein P53) • CD8 (cluster of differentiation 8)
|
TP53 overexpression
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pfifteloxin (OBP-702)
over2years
Modulation of p53 expression in cancer-associated fibroblasts prevents peritoneal metastasis of gastric cancer. (PubMed, Mol Ther Oncolytics)
Combination therapy using intraperitoneal administration of OBP-702 and paclitaxel synergistically inhibited the tumor growth of peritoneal metastases and decreased CAFs in peritoneal metastases. OBP-702, a replicative oncolytic adenovirus-mediated p53 gene therapy, offers a promising biological therapeutic strategy for peritoneal metastasis, modulating CAFs in addition to achieving tumor lysis.
Journal
|
TP53 (Tumor protein P53) • IL6 (Interleukin 6)
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TP53 wild-type • TP53 expression
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paclitaxel • pfifteloxin (OBP-702)
over3years
Oncolytic virotherapy reverses chemoresistance in osteosarcoma by suppressing MDR1 expression. (PubMed, Cancer Chemother Pharmacol)
Our results suggest that MDR1 is an attractive therapeutic target for chemoresistant OS. Tumor-specific virotherapy is thus a promising strategy for reversing chemoresistance in OS patients via suppression of MDR1 expression.
Journal • Oncolytic virus
|
TP53 (Tumor protein P53) • ABCB1 (ATP Binding Cassette Subfamily B Member 1)
|
TP53 expression
|
doxorubicin hydrochloride • pfifteloxin (OBP-702)
over4years
Elimination of MYCN-Amplified Neuroblastoma Cells by Telomerase-Targeted Oncolytic Virus via MYCN Suppression. (PubMed, Mol Ther Oncolytics)
OBP-301 and OBP-702 significantly suppressed the growth of subcutaneous CHP-134 tumors. Thus, these hTERT-driven oncolytic adenoviruses are promising antitumor agents for eliminating MYCN-amplified NB cells via E2F1-mediated suppression of MYCN protein.
Journal
|
TP53 (Tumor protein P53) • TERT (Telomerase Reverse Transcriptase) • MYCN (MYCN Proto-Oncogene BHLH Transcription Factor) • E2F1 (E2F transcription factor 1)
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MYCN amplification
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Telomelysin (suratadenoturev) • pfifteloxin (OBP-702)
over4years
Oncolytic Virus-Mediated Targeting of the ERK Signaling Pathway Inhibits Invasive Propensity in Human Pancreatic Cancer. (PubMed, Mol Ther Oncolytics)
Here, we demonstrate the therapeutic potential of telomerase-specific oncolytic adenoviruses, OBP-301 and tumor suppressor p53-armed OBP-702, against human PDAC cells. Moreover, noninvasive whole-body imaging analyses showed that OBP-702 significantly suppressed tumor growth in an orthotopic PDAC xenograft model, although both viruses were equally effective against subcutaneous tumors, suggesting that OBP-702 can influence the orthotopic tumor microenvironment. Our data suggest that oncolytic virus-mediated disruption of ERK signaling is a promising antitumor strategy for attenuating the invasiveness of PDAC cells.
Journal
|
KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53)
|
KRAS expression
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Telomelysin (suratadenoturev) • pfifteloxin (OBP-702)
over4years
Bone and Soft-Tissue Sarcoma: A New Target for Telomerase-Specific Oncolytic Virotherapy. (PubMed, Cancers (Basel))
OBP-702 exhibits a profound antitumor effect in OBP-301-resistant sarcoma cells via activation of the p53 signaling pathway. Taken together, telomerase-specific oncolytic adenoviruses are promising antitumor reagents that are expected to provide novel therapeutic options for the treatment of bone and soft-tissue sarcomas.
Review • Journal
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TP53 (Tumor protein P53)
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Telomelysin (suratadenoturev) • pfifteloxin (OBP-702)