Delving into the Latest Updates on G-114 with Synapse

Overview

Basic Info

Drug Type

Synthetic peptide

Synonyms

Target-

Mechanism-

Therapeutic Areas

NeoplasmsUrogenital Diseases

Active Indication-

Inactive Indication

Prostatic Cancer

Originator Organization

Rebus Holdings, Inc.

Active Organization-

Inactive Organization

Rebus Holdings, Inc.

Drug Highest PhasePendingDiscovery

First Approval Date-

Regulation-

Author: Milton, Yuka ; Bhowmick, Neil ; Rosen, David Marc ; Isaacs, John T ; Joshi, Nitin ; Safaee, Helia ; Brennen, W Nathaniel ; Karp, Jeffrey M ; Levy, Oren ; Han, Edward ; Ranganath, Sudhir ; Ngai, Jessica ; Musabeyezu, Juliet ; Bhagchandani, Sachin H ; Heinelt, Martina ; Denmeade, Samuel R ; Wang, Hao

Despite considerable advances in prostate cancer research, there is a major need for a systemic delivery platform that efficiently targets anti-cancer drugs to sites of disseminated prostate cancer while minimizing host toxicity. In this proof-of-principle study, human mesenchymal stem cells (MSCs) were loaded with poly(lactic-co-glycolic acid) (PLGA) microparticles (MPs) that encapsulate the macromolecule G114, a thapsigargin-based prostate specific antigen (PSA)-activated prodrug. G114-particles (∼950 nm in size) were internalized by MSCs, followed by the release of G114 as an intact prodrug from loaded cells. Moreover, G114 released from G114 MP-loaded MSCs selectively induced death of the PSA-secreting PCa cell line, LNCaP. Finally, G114 MP-loaded MSCs inhibited tumor growth when used in proof-of-concept co-inoculation studies with CWR22 PCa xenografts, suggesting that cell-based delivery of G114 did not compromise the potency of this pro-drug in-vitro or in-vivo. This study demonstrates a potentially promising approach to assemble a cell-based drug delivery platform, which inhibits cancer growth in-vivo without the need of genetic engineering. We envision that upon achieving efficient homing of systemically infused MSCs to cancer sites, this MSC-based platform may be developed into an effective, systemic 'Trojan Horse' therapy for targeted delivery of therapeutic agents to sites of metastatic PCa.

100 Deals associated with G-114

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