Request Demo

Last update 08 May 2025

MSLN x FASN

Last update 08 May 2025

Basic Info

Related Targets

MSLNFASN

Drugs associated with MSLN x FASN

AB-1015

Target

FASN x MSLN

Mechanism

FAS inhibitors [+1]

Active Org.

Arsenal Biosciences, Inc.

Originator Org.

Arsenal Biosciences, Inc.

Active Indication

Fallopian Tube Carcinoma [+4]

Inactive Indication-

Drug Highest PhasePhase 1

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

Clinical Trials associated with MSLN x FASN

NCT05617755

/ Active, not recruitingPhase 1

An Open-label Phase 1 Study to Evaluate the Safety and Efficacy of AB-1015 in Patients with Resistant/Refractory Epithelial Ovarian Cancer

This is a multi-center, open-label phase 1 dose escalation trial that uses a modified 3+3 design to identify a recommended phase 2 dose (RP2D) of AB-1015 cell product. Backfill cohorts will enroll additional subjects at doses deemed to be safe for a total enrollment of up to 12 subjects per each backfill cohort on the protocol.

Start Date29 Nov 2022

Sponsor / Collaborator

Arsenal Biosciences, Inc.

100 Clinical Results associated with MSLN x FASN

100 Translational Medicine associated with MSLN x FASN

0 Patents (Medical) associated with MSLN x FASN

Literatures (Medical) associated with MSLN x FASN

01 Jan 2023·Juntendo Medical Journal

A Surgeon Involved in Basic Research - on the Occasion of Studying Abroad

Article

Author: ITO, TOMOAKI

I, the author, expressed gratitude for receiving the 45^th Juntendo Medical School Alumni Association Academic Encouragement Award in May 2023. After completing medical school and surgical training at Juntendo University, I embarked on a new challenge by pursuing a Ph.D. in basic clinical research, with a focus on gastric cancer, the third leading cause of cancer related death in Japan. Collaborating with various experts, I obtained a Ph.D. in cancer research studies in 2014. Subsequently, I pursued further research opportunities in the United States, where I undertook multiple projects focusing on cancer and maternal stress. I would like to present several studies, ERC/mesothelin, fatty acid synthase, and maternal stress in this manuscript. On returning to clinical practice at Juntendo University Shizuoka Hospital in 2019, I developed an interest in various clinical issues and decided to address these through experiments. In collaborating with several researchers at the Shizuoka Medical Research Center for Disasters, our ongoing research aims to answer several clinical questions. Furthermore, I aspire to guide junior staff in the future and am grateful for the invaluable connections and opportunities provided by Juntendo University.

15 Jun 2022·Cancer Research

Abstract 585: AB-1015, a novel integrated circuit T cells containing an ALPG/MSLN logic gate and FAS/PTPN2 shRNA-miR, demonstrates specific and potent activity against ALPG/MSLN tumors

Author: Haining, W. Nicholas ; Jun, Susie ; McDevitt, Jennifer ; Bezman, Natalie ; Cooper, Aaron ; Chawla, Kanika ; Santoro, Stephen ; Feng, Jun ; Mikkelsen, Tarjei

AbstractIn solid tumors, CAR T cell efficacy is limited by off-tumor toxicity, poor persistence, and suppression by the tumor microenvironment (TME). To address these challenges we have engineered AB-1015, an integrated circuit T cell (ICT cell) intended for the treatment of ovarian cancer. The AB-1015 transgene cassette encodes an “AND” logic gate designed to limit off-tumor toxicity through dual tumor antigen recognition and a dual shRNA-miR to resist TME suppression and improve ICT cell function and persistence. The AB-1015 DNA cassette is inserted into the T cell genome at a defined novel genomic site via CRISPR-based gene editing. The AB-1015 logic gate consists of a priming receptor that induces expression of an anti-mesothelin (MSLN) CAR upon engagement of a ALPG/P (alkaline phosphatase germ-line/placental). The dual-antigen specificity of the logic gate was assessed in mice engrafted with MSLN+ and ALPG/P+MSLN+ K562 tumors established on contralateral flanks. AB-1015 ICT cells eliminated ALPG/P+MSLN+ tumors, while sparing tumors that lacked ALPG/P. To assess the ability of AB-1015 to mediate killing of MSLN+ tumor cells in the context of heterogeneous cultures, we utilized an admixed co-culture system where ALPG/P+ target cells were spiked into cultures that were otherwise MSLN+. AB-1015 was able to eliminate admixed co-cultures where as few as 5-15% of the target cells expressed ALPG/P.The AB-1015 also contains a dual shRNA-miR that targets FAS and PTPN2, two critical mediators of T cells survival and function. FASL, the cognate ligand for FAS receptor, is expressed on the surface of activated T cells and is significantly overexpressed in the ovarian cancer TME. In vitro, AB-1015 demonstrated resistance to FAS-mediated apoptosis. Knockdown of PTPN2, a phosphatase involved in T cell proliferation and functional persistence, resulted in enhanced AB-1015 ICT cell expansion during repetitive stimulation over a period of 14 days, as well as a 30-fold reduction in tumor outgrowth compared with logic gated T cells alone. In summary, AB-1015 ICT cells are specific for ALPG/P+MSLN+, demonstrate superior potency, expansion, and persistence compared with logic gated T cells alone, and are resistant to ovarian TME suppression. These results support further evaluation of AB-1015 as a novel therapy for indications including ovarian, fallopian tube, or primary peritoneal cancer.Citation Format: Stephen Santoro, Aaron Cooper, Natalie Bezman, Jun Feng, Kanika Chawla, Jennifer McDevitt, Tarjei Mikkelsen, Susie Jun, W. Nicholas Haining. AB-1015, a novel integrated circuit T cells containing an ALPG/MSLN logic gate and FAS/PTPN2 shRNA-miR, demonstrates specific and potent activity against ALPG/MSLN tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 585.

31 Dec 2009·Future OncologyQ4 · MEDICINE

Pathogenesis of Ovarian Cancer: Clues from Selected Overexpressed Genes

Q4 · MEDICINE

Review

Author: Davidson, Ben ; Shih, Ie-Ming

Ovarian cancer is the most malignant gynecologic neoplasm. Although new chemotherapeutic agents have improved patients’ 5-year survival rate, the overall mortality of ovarian cancer has remained largely unchanged in the past several decades. The main reason for the lack of success in effectively treating ovarian cancer is our limited understanding of its etiology and the very few molecular diagnostic markers and therapeutic targets known so far. Identification and characterization of ovarian cancer-associated genes are fundamental for unveiling the pathogenesis of its initiation and progression, especially the development of recurrent diseases. As there are a vast number of genes for which molecular genetic changes and aberrant gene expression have been reported in ovarian cancer, this review will only focus on summarizing those exemplified genes that have been demonstrated to have biological functions in promoting ovarian cancer development and potential clinical significance. The genes to be discussed include nuclear proteins (Notch3, HBXAP [Rsf-1], NAC1 and NFκB), cytoplasmic proteins (fatty acid synthase and apolipoprotein E) and cell surface/secretory proteins (mucin-4, mesothelin, claudin, HLA-G, kallikrein and folate receptor and osteopontin). Since the study of ovarian cancer-associated genes is complicated by several factors unique to ovarian cancer, we will also present our views on the limitations and challenges of current ovarian cancer research.

Analysis

Perform a panoramic analysis of this field.

view full example data

Chat with Hiro

Get started for free today!

Accelerate Strategic R&D decision making with Synapse, PatSnap’s AI-powered Connected Innovation Intelligence Platform Built for Life Sciences Professionals.

Start your data trial now!

Synapse data is also accessible to external entities via APIs or data packages. Empower better decisions with the latest in pharmaceutical intelligence.

Bio

Bio Sequences Search & Analysis

Chemical

Chemical Structures Search & Analysis