Delving into the Latest Updates on MSLN-CAR.CIK with Synapse

Overview

Basic Info

Drug Type

CIK therapy

Synonyms-

Target

MSLN

Mechanism

MSLN modulators(Mesothelin modulators)

Therapeutic Areas

NeoplasmsDigestive System DisordersOther Diseases

Active Indication

Bile Duct Neoplasms

Inactive Indication-

Originator Organization

University of Turin

Active Organization

University of Turin

Inactive Organization-

Drug Highest PhasePreclinical

First Approval Date-

Regulation-

Author: Donini, Chiara ; Galvagno, Federica ; Proment, Alessia ; Sangiolo, Dario ; Vitali, Letizia ; Massa, Annamaria ; D'Ambrosio, Lorenzo ; D’Ambrosio, Lorenzo ; Primo, Luca ; Capellero, Sonia ; Rotolo, Ramona ; Vigna, Elisa ; Valabrega, Giorgio ; Merlini, Alessandra ; Lombardi, Andrea Maria ; Leuci, Valeria ; Tuninetti, Valentina ; Puliafito, Alberto

Intraperitoneal cellular immunotherapy with CAR-redirected lymphocytes is an intriguing approach to target peritoneal carcinomatosis (PC) from ovarian cancer (OC), which is currently evaluated in clinical trials. PC displays a composite structure with floating tumor cells within ascites and solid-like masses invading the peritoneum. Therefore, a comprehensive experimental model is crucial to optimize CAR-cell therapies in such a peculiar environment. Here, we explored the activity of cytokine-induced killer lymphocytes (CIK), redirected by CAR against mesothelin (MSLN-CAR.CIK), within reductionistic 3D models resembling the structural complexity of both liquid and solid components of PC. MSLN-CAR.CIK effectively killed and were functionally efficient against OC targets. In a "floating-like" 3D context with floating OC spheroids, both tumor localization and killing by MSLN-CAR.CIK were significantly boosted by fluid flow. In a "solid-like" context, MSLN-CAR.CIK were recruited through the extracellular matrix on embedded tumor aggregates, with variable kinetics depending on the effector-target distance. Furthermore, MSLN-CAR.CIK penetrated the inner levels of OC spheroids exerting effective tumor killing. Our findings provide currently unknown therapeutically relevant information on intraperitoneal approaches with CAR.CIK, supporting further developments and improvements for clinical studies in the context of locoregional cell therapy approaches for patients with PC from OC.

100 Deals associated with MSLN-CAR.CIK

Login to view more data