Delving into the Latest Updates on 4-1BB targeted oncolytic measles virus (Themis Bio) with Synapse

Overview

Basic Info

Drug Type

Oncolytic virus

Synonyms

s4-1BBL-TriXVII

Target

4-1BB

Action

agonists

Mechanism

4-1BB agonists(Tumor necrosis factor receptor superfamily member 9 agonists)

Therapeutic Areas

Neoplasms

Active Indication

Neoplasms

Inactive Indication-

Originator Organization

Themis Bioscience GmbH

Active Organization

Themis Bioscience GmbH

Inactive Organization-

Drug Highest PhasePreclinical

First Approval Date-

Regulation-

AbstractTargeting co-stimulatory receptors promotes the activation and effector functions of anti-tumor lymphocytes. 4-1BB (CD137/TNFSF9), a member of the tumor necrosis factor receptor superfamily (TNFR-SF), is a potent co-stimulatory receptor that plays a prominent role in augmenting effector functions of CD8+T cells, but also CD4+T cells and NK cells. Agonistic antibodies against 4-1BB have entered clinical trials and shown signs of therapeutic efficacy. Here, we have used a T cell reporter system to evaluate various formats of 4-1BBL regarding their capacity to functionally engage its receptor. We found that a secreted 4-1BBL ectodomain harboring a trimerization domain derived from human collagen (s4-1BBL-TriXVIII) is a strong inducer of 4-1BB co-stimulation. Similar to the 4-1BB agonistic antibody urelumab, s4-1BBL-TriXVIIIis very potent in inducing CD8+and CD4+T cell proliferation. We provide first evidence that s4-1BBL-TriXVIIIcan be used as an effective immunomodulatory payload in therapeutic viral vectors. Oncolytic measles viruses encoding s4-1BBL-TriXVIIIsignificantly reduced tumor burden in a CD34+humanized mouse model, whereas measles viruses lacking s4-1BBL-TriXVIIIwere not effective. Natural soluble 4-1BB ligand harboring a trimerization domain might have utility in tumor therapy especially when delivered to tumor tissue as systemic administration might induce liver toxicity.

100 Deals associated with 4-1BB targeted oncolytic measles virus (Themis Bio)

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