Delving into the Latest Updates on PFI-103 with Synapse

Overview

Basic Info

Drug Type

Monoclonal antibody

Synonyms

anti-FSTL1 mAbs (National Cancer Center)

Target

FSTL1

Mechanism

FSTL1 inhibitors(Follistatin related protein 1 inhibitors)

Therapeutic Areas

NeoplasmsSkin and Musculoskeletal DiseasesOther Diseases

Active Indication-

Inactive Indication

OsteosarcomaSolid tumor

Originator Organization

Japanese National Cancer Center

Active Organization-

Inactive Organization

Pharma Foods International Co., Ltd.Japanese National Cancer Center

Drug Highest PhaseDiscontinuedPreclinical

First Approval Date-

Regulation-

Monoclonal antibodies (mAbs), successfully adopted in the treatment of several haematological malignancies, have proved almost ineffective in multiple myeloma (MM), because of the lack of an appropriate antigen for targeting and killing MM cells. Here, we demonstrate that PSGL1, the major ligand of P-Selectin, a marker of plasmacytic differentiation expressed at high levels on normal and neoplastic plasma cells, may represent a novel target for mAb-mediated MM immunotherapy. The primary effectors of mAb-induced cell-death, complement-mediated lysis (CDC) and antibody-dependent cell-mediated cytotoxicity (ADCC), were investigated using U266B1 and LP1 cell-lines as models. Along with immunological mechanisms, the induction of apoptosis by PSGL1 cross-linking was assessed. The anti-PSGL1 murine mAb KPL1 induced death of MM cells in a dose- and time-dependent fashion and mediated a significant amount of ADCC. KPL1 alone mediated C1q deposition on target cells but proved unable to induce CDC due to inhibition of the lytic activity of complement by membrane complement regulators (mCRP) expressed on the cell surface. Consistently, CDC was induced by KPL1 upon mCRP blockage. Our results suggest a role for PSGL1 in MM humoral immunotherapy and support further in vivo studies assessing the effects of anti-PSGL1 mAbs on MM growth and interaction with the bone marrow microenvironment.

100 Deals associated with PFI-103

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Osteosarcoma	Preclinical	JP	Pharma Foods International Co., Ltd.	-
Solid tumor	Preclinical	JP	Pharma Foods International Co., Ltd.	-
Solid tumor	Preclinical	JP	Japanese National Cancer Center	-