Delving into the Latest Updates on GEN-0101 with Synapse

The preliminary study revealed that the ethyl acetate eluate of Youngia japonica (YJ-E) could inhibit the expression of key proteins of p-p65, p-IκBα, p-IKKα/β, and p-AKT in LPS stimulated BV2 cell. Further phytochemical study led to the isolation of eight compounds from YJ-E, including one new sesquiterpene lactone. Their structures were elucidated by several spectroscopic data, and comparing the NMR data of known compound. In addition, all of the isolates were evaluated for the anti-inflammatory effect. As a result, compounds 3 and 4 distinctly attenuated the expressions of p-IκBα, p-p65, and p-AKT in LPS stimulated BV2 cell, respectively.

01 Dec 2024·Molecular Therapy: Oncology

Local treatment of HVJ-E with T cell costimulatory molecule stimulation elicits systemic anti-tumor effects

Article

Author: Kitamura, Koji ; Hashimoto, Shinichi ; Yagita, Hideo ; Ohashi, Riuko ; Saga, Kotaro ; Kaneda, Yasufumi ; Uegaki, Yuko ; Ohta, Noriko ; Ishida, Kyoso ; Hisatomi, Yuuta ; Kiyohara, Eiji ; Yoshimura, Yasuhide ; Iwabuchi, Sadahiro ; Li, Yue ; Nimura, Keisuke ; Inubushi, Satoko ; Tanemura, Atsushi ; Ishibashi, Airi

The tumor-infiltrating lymphocyte (TIL) is a crucial factor in controlling tumor growth. A therapeutic method activating TIL is desired for treating patients with metastatic tumors. Here, we show that treating a local tumor with a combination therapy of UV-irradiated hemagglutinating virus of Japan envelope (HVJ-E) plus agonist antibodies, including OX40, against T cell costimulatory molecules induces systemic anti-tumor effects in a T cell-dependent manner in multiple cancer cell lines. Transcriptome and T cell receptor repertoire analyses revealed that HVJ-E + anti-OX40 antibody treatment activates CD4 and CD8 T cells and promotes T cell trafficking between tumors. These systemic anti-tumor effects required an association between Nkg2d and Nkg2d ligands. Our findings provide insights into how systemic anti-tumor effects are induced and may help the development of therapeutic strategies for eliciting such effects.

12 Jan 2024·Reproduction

The press-assisted fusion scheme significantly mitigates the quantity of HVJ-E required in mitochondrial replacement techniques

Article

Author: Lyu, Qifeng ; Lin, Kaibo ; Li, Danjun ; Liao, Xiaoyu ; Chen, Chen ; Jiang, Shutian ; Kuang, Yanping ; Ma, Meng ; Li, Wenzhi ; Jin, Wei

In briefThe impact of HVJ-E employed in mitochondrial replacement techniques (MRTs) on embryonic development remains uncertain. This study has exhibited the influence of HVJ-E utilized in MRTs on embryonic development and has devised a novel HVJ-E-induced fusion approach to curtail the amount of HVJ-E employed in MRTs.AbstractMitochondrial replacement techniques (MRTs) provide a viable option for women carrying pathogenic mitochondrial DNA (mtDNA) variants to conceive disease-free offspring with a genetic connection. In comparison to electrofusion, HVJ-E-induced fusion has been identified as the most promising approach for clinical translation of MRTs due to its absence of electrical interference. However, despite confirmation of the absence of RNA activity in HVJ-E, a reduction in blastocyst quality has been observed in various MRTs studies utilizing the HVJ-E-induced fusion scheme. Recent investigations have revealed a dose-dependent elevation of reactive oxygen species (ROS) levels in various cancer cells incubated with HVJ-E. However, the impact of HVJ-E as a sole determinant on embryonic development in MRTs remains unverified. This investigation establishes that the augmented concentration of HVJ-E utilized in the conventional HVJ-E fusion protocol is an autonomous variable that influences embryonic development in MRTs. This effect may be attributed to amplified DNA damage resulting from heightened levels of ROS in reconstructed embryos. To mitigate the presence of HVJ-E in reconstructed zygotes while maintaining optimal fusion efficiency in MRTs, a novel HVJ-E-induced fusion approach was devised, namely, press-assisted fusion. This technique offers potential advantages in reducing detrimental factors that impede embryo development in MRTs.

100 Deals associated with GEN-0101

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Indication	Highest Phase	Country/Location	Organization	Date
Melanoma	Phase 2	-	TSD Japan, Inc.	-
Mesothelioma	Phase 2	-	ISHIHARA SANGYO KAISHA LTD.	-
Mesothelioma	Phase 2	-	TSD Japan, Inc.	-
Mesothelioma	Phase 2	-	Osaka University	-
Prostatic Cancer	Phase 2	-	ISHIHARA SANGYO KAISHA LTD.	-
Prostatic Cancer	Phase 2	-	Osaka University	-
Prostatic Cancer	Phase 2	-	TSD Japan, Inc.	-
Locally Advanced Melanoma	Discovery	JP	Osaka University	01 Mar 2019
Locally Advanced Melanoma	Discovery	JP	ISHIHARA SANGYO KAISHA LTD.	01 Mar 2019
Castration-Resistant Prostatic Cancer	Discovery	JP	Osaka University	01 May 2015