Here we have evaluated the anti-tumor effects of trimerized membrane-bound (TMZ)-CD40L-armed LOAd700 and TMZ-CD40L/4-1BBL-armed LOAd703 in a variety of solid tumors to understand the underlying tumor modulating mechanisms. Upregulation of cell surface calreticulin as well as the death receptors TRAIL-R1 and -R2 indicated generation of a more immunogenic phenotype of cancer cells. Thus, our findings suggest that CD40L-armed LOAd viruses could be inducers of apoptosis and immunogenic cell death in a variety of cancer types with an augmented effect in cancer cells expressing the CD40 receptor.

2 years ago

Oncolytic virus • IO biomarker

CASP3 (Caspase 3) • TNFRSF10A (TNF Receptor Superfamily Member 10a) • CALR (Calreticulin) • CASP7 (Caspase 7) • CD40LG (CD40 ligand) • TNFRSF10B (TNF Receptor Superfamily Member 10b) • HSP90AA1 (Heat Shock Protein 90 Alpha Family Class A Member 1Heat Shock Protein 90 Alpha Family Class A Member 1)

LOAd700 • delolimogene mupadenorepvec (LOAd703)

4years

Immunostimulatory oncolytic virotherapy for multiple myeloma targeting 4-1BB and/or CD40. (PubMed, Cancer Gene Ther)

Further, LOAd viruses are armed with human immunostimulatory transgenes: trimerized membrane-bound CD40L (LOAd700, LOAd703) and 4-1BBL (LOAd703). This was most prominent with LOAd703. In conclusion, LOAd viruses are of interest for MM therapy.

4 years ago

Journal

CXCL10 (Chemokine (C-X-C motif) ligand 10) • CD70 (CD70 Molecule) • ICAM1 (Intercellular adhesion molecule 1) • CCL2 (Chemokine (C-C motif) ligand 2) • CD40LG (CD40 ligand)

LOAd700 • delolimogene mupadenorepvec (LOAd703)