Delving into the Latest Updates on PGV-001 with Synapse

Overview

Basic Info

Drug Type

Personalized antigen vaccine, Therapeutic vaccine

Synonyms-

Target

TLR3

Action

agonists

Mechanism

TLR3 agonists(Toll like receptor 3 agonists)

Therapeutic Areas

NeoplasmsUrogenital Diseases

Active Indication

Prostate Cancer, Hereditary, 7

Inactive Indication

Advanced Malignant Solid NeoplasmBladder CancerLocally Advanced Urothelial Carcinoma

Originator Organization

Icahn School of Medicine at Mount Sinai

Active Organization

Icahn School of Medicine at Mount Sinai

Inactive Organization

Genentech, Inc.

License Organization-

Drug Highest PhasePhase 1

First Approval Date-

Regulation-

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The purpose of this study is to determine the good and bad effects of atezolizumab given in combination with a personalized cancer vaccine in patients with urothelial cancer either after surgery to remove organ where the tumor arose (for example, removal of the bladder) or for urothelial cancer that has spread to other organs.

Start Date08 May 2019

Sponsor / Collaborator

Icahn School of Medicine at Mount Sinai

[+1]

NCT02721043

/ CompletedPhase 1IIT

Study Of Pgv001 A Multi-Peptide Therapeutic Vaccine Platform For Use In The Treatment Of Malignancies In The Adjuvant Setting

The purpose of this study is to test the safety, tolerability, and immunogenicity of Personalized Genomic Vaccine 001 (PGV001) in subjects with advanced non-hematologic malignancies. PGV001 is a peptide vaccine that is based on a patient's own tumor sequence. Each patient's tumor is sequenced and peptides that correspond to the tumors are made. These peptides combined with the adjuvant Poly-ICLC (Hiltonol®, Oncovir) make PGV001. The adjuvant Poly-ICLC is added to boost the immune response to the peptides and together will expand immune cells to target cancer.

Start Date01 Apr 2016

Sponsor / Collaborator

Icahn School of Medicine at Mount Sinai

100 Clinical Results associated with PGV-001

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100 Translational Medicine associated with PGV-001

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100 Patents (Medical) associated with PGV-001

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15

Literatures (Medical) associated with PGV-001

10 Oct 2024·Advanced Pharmaceutical Bulletin

PGV-1 Causes Disarrangement of Spindle Microtubule Organization Resulting in Aberrant Mitosis in HLF and HuH6 Cells Associated with Altered MYCN Status

Article

Author: Hippo, Yoshitaka ; Hapsari, Novia Permata ; Lestari, Beni ; Ikawati, Muthi ; Meiyanto, Edy ; Zulfin, Ummi Maryam ; Nugraheni, Nadzifa ; Utomo, Rohmad Yudi ; Suenaga, Yusuke

Purpose: The HLF and HuH-6 cell lines represent hepatocellular carcinoma (HCC) with different characteristics in chromosome content that may give different drug responses. Here, PGV-1 was intended to challenge the growth-suppressing effect on HLF and HuH-6 and trace the molecular target mechanism of action compared to sorafenib. Methods: We applied MTT cytotoxic assay, colony forming assay, flow cytometry analysis, immunofluorescence assay and western blot assay. Results: PGV-1 exhibited cytotoxic effects on HLF and HuH-6 with IC-50 values of 1 µM and 2 µM, respectively, whereas sorafenib showed less cytotoxicity with IC-50 values of 5 µM and 8 µM respectively. PGV-1 suppressed the cell growth permanently but not for sorafenib. Sorafenib did not change the cell cycle profiles on both cells, but PGV-1 arrested the cells at G2/M with the characteristic of senescent cells and mitotic disarrangement. PGV-1 and sorafenib showed the same effect in downregulating p-EGFR, indicating that both compounds have the same target on EGFR activation or as Tyrosine kinase inhibitors. PGV-1 suppressed the MYCN expression in HuH-6 and HLF cells but stabilized cMYC-T58 indicating that even though the MYCN was downregulated, the cells maintained the active form of cMYC. In this regard, PGV-1 also stabilized the expression of PLK-1 and AurA. Conclusion: PGV-1 elicits stronger cytotoxic properties compared to sorafenib. The lower the MYCN expression, the higher the cytotoxic effect of PGV-1. PGV-1 abrogates cell cycle progression of both cells in mitosis through EGFR inhibition and stabilizes PLK-1 and AurA in correlation with the suppression of MYCN expression.

01 Jan 2024·Saudi Pharmaceutical Journal

Pentagamavunone-1 inhibits aggressive breast cancer cell proliferation through mitotic catastrophe and ROS-mediated activities: in vitro and in vivo studies

Article

Author: Yoneda-Kato, Noriko ; Nakamae, Ikuko ; Istighfari Jenie, Riris ; Meiyanto, Edy ; Kato, Jun-Ya ; Novitasari, Dhania

Pentagamavunone-1 (PGV-1), an analog of curcumin, has been studied for its cytotoxic effects in 4T1, MCF7, MCF7/HER2, and T47D breast cancer cells. Its antiproliferative effect is partly mediated through G2/M arrest; however, its molecular mechanism during cell cycle progression remains unknown. In this study, we aimed to determine whether PGV-1 has any anticancer effects on highly aggressive breast cancer cells, with a focus on cell cycle regulatory activity, reactive oxygen species (ROS) generation, and their mediated effects on cancer cells. MDA-MB-231 (triple-negative) and HCC1954 (overexpressed HER2) immortalized human breast cancer cells were used in the study. PGV-1 exhibited cytotoxic activity with an irreversible antiproliferative impact on treated cells and had good selectivity when tested in fibroblast cells. Oral PGV-1 administration suppressed tumor growth in a cell-derived xenograft mouse model. PGV-1 induced the phosphorylation of Aurora A kinase and PLK1 in MDA-MB-231 cells, while PLK1 and cyclin B1 phosphorylation were enhanced in the PGV-1-treated HCC1954 cells during prometaphase arrest. Intracellular ROS production was substantially higher upon PGV-1 treatment following mitotic arrest, and this activity caused impairment of mitochondrial respiration, induced senescence, and subsequently triggered early-to-late apoptosis. Collectively, these results suggest that the molecular mechanism of PGV-1 involves the regulation of mitotic kinases to cause cell cycle arrest and the enhancement of ROS production to impair mitochondrial activity and induce cellular senescence. The therapeutic activities demonstrated by PGV-1 in this study show its potential as an appealing candidate for chemotherapy in breast cancer treatment.

01 Oct 2023·Journal of Advanced Pharmaceutical Technology & Research

Tumour‐suppressive effects of curcumin analogs CCA‐1.1 and Pentagamavunone‐1 in colon cancer: In viv o and in vitro studies

Article

Author: Ikawati, Muthi ; Wulandari, Febri ; Meiyanto, Edy ; Kirihata, Mitsunori ; Kato, Jun-ya ; Novitasari, Dhania ; Widyarini, Sitarina

This study aimed to evaluate the efficacy of Chemoprevention Curcumin Analog-1.1 (CCA-1.1) and Pentagamavunone-1 (PGV-1) in vivo and in vitro in colorectal cancer model. CCA-1.1 or PGV-1 was administered orally to 1,2-dimethylhydrazine (DMH)-induced rats for 16 weeks. The cytotoxicity of both compounds was tested on Caco-2, CT26, and NIH/3T3 cells using the MTT method. The cell cycle, apoptosis, and reactive oxygen species (ROS) levels were analyzed through flow cytometry. X-gal staining was used to examine the compound’s effect on senescence. Oral co-administration of CCA-1.1 or PGV-1 significantly suppressed the carcinogenic characteristics and symptoms of premalignant colon cancer relative to DMH-only and untreated groups. CCA-1.1 and PGV-1 administration did not affect the blood profile. CCA-1.1 and PGV-1 demonstrated great cytotoxicity on Caco-2 and CT26 cells, with 50% inhibition concentration (IC50) values of 4.3 ± 0.2 and 3.1 ± 0.1 µM for CCA-1.1 and 11.2 ± 1.1 and 4.8 ± 0.1 µM for PGV-1, respectively, while not toxic against fibroblast cells. Both compounds instigated G2/M arrest and efficiently induced cell senescence and apoptosis. Moreover, these analogs selectively elevated oxidative stress in colon cancer cells without inducing noticeable changes in fibroblasts. In conclusion, PGV-1 and CCA-1.1 suppressed colorectal tumor formation and induced mitotic arrest.

100 Deals associated with PGV-001

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Bladder Cancer	NDA/BLA	United States	Genentech, Inc.	08 May 2019
Locally Advanced Urothelial Carcinoma	NDA/BLA	United States	Genentech, Inc.	08 May 2019
Advanced Malignant Solid Neoplasm	NDA/BLA	United States	Icahn School of Medicine at Mount Sinai	01 Apr 2016
Prostate Cancer, Hereditary, 7	Phase 1	United States	Icahn School of Medicine at Mount Sinai	05 Jan 2022

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT02721043 (Pubmed \| Cancer Discov) Manual	Phase 1	Solid tumor \| Hematologic Neoplasms Adjuvant	11	PGV001	(lwmkurvsen) = 100% of vaccinated patients developed targeted T cell and B cell responses highlighting the capacity of OpenVax to predict immunogenic neoantigens and the potential of PGV001 for safely inducing targeted immunity. jbbcldepew (adytchpnof )	Positive	17 Mar 2025
NCT03359239 (AACR2024) Manual	Phase 1	Transitional Cell Carcinoma Adjuvant	9	Atezolizumab plPGV-001001	lwnlnqpgtn(ugqxfvgkay) = nuwgnxzhjo adajkodumc (xwswshemxv ) View more	Positive	05 Apr 2024
NCT02721043 (AACR2023) Manual	Phase 1	Neoplasms	13	PGV-001	(tmzfwcgrsw) = reached xhawiuyouq (zdrozaqvvc ) Met View more	Positive	14 Apr 2023
NCT02721043 (PGV-001, AACR2021)	Phase 1	Neoplasms Adjuvant	15	PGV-001	ezmkvrijbm(bgfsxmnbkn) = oiihkkknaz fcsemziqbh (cbspqalqhi ) View more	-	01 Jul 2021