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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
3d
Combined Efficacy of Dendritic Cell Vaccine and Oncolytic Adenovirus in Colorectal Cancer (PubMed, Gan To Kagaku Ryoho)
We have developed an oncolytic adenovirus OBP-702 carrying the tumor suppressor gene p53 and have demonstrated its therapeutic potential to induce cytopathic effect and activate antitumor immunity via p53 induction. In this study, we investigated the combined effect of p53-transduced DC vaccine and OBP-702 in colorectal cancer.
Journal • Oncolytic virus
|
TP53 (Tumor protein P53)
|
pfifteloxin (OBP-702)
19d
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)
4ms
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)
10ms
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)
1year
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
|
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)
|
TP53 wild-type • TP53 expression
|
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)
|
MYCN amplification
|
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)
almost5years
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)
|
Telomelysin (suratadenoturev) • pfifteloxin (OBP-702)