Combination of immunogenic oncolytic adenovirus ONCOS-102 with anti-PD-1 pembrolizumab exhibits synergistic antitumor effect in humanized A2058 melanoma huNOG mouse model.

Combination of immunogenic oncolytic adenovirus ONCOS-102 with anti-PD-1 pembrolizumab exhibits synergistic antitumor effect in humanized A2058 melanoma huNOG mouse model.

Publication date: Jun 27, 2018

Malignant melanoma is an aggressive type of skin cancer whose incidence is increasing globally. Although surgery is effective in early stage melanoma, patients with advanced melanoma only have a 20% 5-year survival rate. Hence, combinations of existing and new immunotherapy technologies and immunotherapeutic agents are being evaluated. ONCOS-102 is an oncolytic adenovirus armed with human GM-CSF and an Ad5/3 chimeric capsid. It has shown to be well tolerated in phase I study (NCT01598129) wherein it induced antitumor immunity, infiltration of CD8 + T cells to tumors, and up-regulation of PD-L1. We propose that ONCOS-102 could serve as an immunosensitizer in combination therapies with checkpoint inhibitors. In this preclinical study, we investigated the cytotoxicity of ONCOS-102 and pembrolizumab, an anti-PD-1 antibody, in four human melanoma cell lines, A375, A2058, SK-Mel-2 and SK-Mel-28. Humanized mice engrafted with A2058 melanoma cells showed significant tumor volume reduction after ONCOS-102 treatment. Combination of pembrolizumab with ONCOS-102 reduced tumor volume to an even greater extent, while pembrolizumab (200 ug, or 400 ug) did not show any therapeutic benefit by itself. Body weight loss, and metastasis were not significantly affected by any treatment. These data support the scientific rationale for the ongoing clinical study of combination therapy of ONCOS-102 and pembrolizumab for the treatment of melanoma (NCT03003676).

Open Access PDF

Kuryk, L., Moller, A.W., and Jaderberg, M. Combination of immunogenic oncolytic adenovirus ONCOS-102 with anti-PD-1 pembrolizumab exhibits synergistic antitumor effect in humanized A2058 melanoma huNOG mouse model. 22265. 2018 Oncoimmunology (8):2.

Concepts Keywords
Antibody Checkpoint inhibitor
Capsid Oncolytic virus
CD8 Pembrolizumab
Chimeric Biotechnology
Combination Therapy Virotherapy
Cytotoxicity Experimental cancer treatments
Immunity Immune system
Immunogenic Cancer treatments
Immunotherapeutic Adenoviridae
Immunotherapy Clinical medicine
Incidence Medicine
Malignant Melanoma Surgery
Melanoma Immunotherapy
Metastasis T tumors
Synergistic Early stage melanoma
Tumor Significant tumor
Weight Loss Antibody melanoma

Semantics

Type Source Name
gene UNIPROT TNF
drug DRUGBANK Paclitaxel
gene UNIPROT OPRM1
drug DRUGBANK Carnosine
disease DOID vaccinia
disease MESH vaccinia
gene UNIPROT ZBP1
gene UNIPROT CD40LG
gene UNIPROT WAPL
pathway BSID Immune System
gene UNIPROT LARGE1
gene UNIPROT CD5
gene UNIPROT MBNL1
gene UNIPROT PSMB6
gene UNIPROT YY1
gene UNIPROT DLL1
pathway BSID Infectious disease
disease DOID infectious disease
disease MESH infectious disease
disease DOID Cancer
gene UNIPROT DUOXA1
drug DRUGBANK Ipilimumab
drug DRUGBANK Ibuprofen
gene UNIPROT CXCL2
gene UNIPROT F11R
gene UNIPROT BRD2
disease DOID kidney cancer
disease MESH kidney cancer
gene UNIPROT PROC
disease MESH B16 melanoma
gene UNIPROT COL9A3
gene UNIPROT COMP
gene UNIPROT COL9A1
gene UNIPROT COL9A2
gene UNIPROT SCN8A
gene UNIPROT SMPD1
disease DOID ASM
gene UNIPROT PDC
gene UNIPROT EGR3
gene UNIPROT PRDM6
disease MESH dissociation
gene UNIPROT HPD
drug DRUGBANK Water
gene UNIPROT TNFSF14
gene UNIPROT COX8A
gene UNIPROT BANK1
gene UNIPROT MAP6
drug DRUGBANK Hydrogen peroxide
gene UNIPROT WASHC1
gene UNIPROT FAM155B
gene UNIPROT TREH
gene UNIPROT MIXL1
gene UNIPROT DECR1
gene UNIPROT SGCG
gene UNIPROT KIT
gene UNIPROT TIMM8A
gene UNIPROT C2
gene UNIPROT TSPO
gene UNIPROT CHRM3
drug DRUGBANK Edetic Acid
drug DRUGBANK Trypsin
drug DRUGBANK Streptomycin
gene UNIPROT IL31RA
gene UNIPROT AMH
gene UNIPROT HLA-C
gene UNIPROT HGS
gene UNIPROT SRSF5
gene UNIPROT HARS
pathway BSID Release
gene UNIPROT DSG1
gene UNIPROT MUC1
disease DOID viral infection
disease MESH viral infection
gene UNIPROT INTU
gene UNIPROT SIGLEC6
gene UNIPROT CD4
gene UNIPROT SLC35G1
gene UNIPROT PTPRC
gene UNIPROT MENT
gene UNIPROT SMIM10L2A
drug DRUGBANK Trestolone
gene UNIPROT SMIM10L2B
gene UNIPROT ATP8A2
drug DRUGBANK ATP
gene UNIPROT SLC6A8
gene UNIPROT CALCR
gene UNIPROT CALR
gene UNIPROT APOPT1
disease DOID noma
disease MESH noma
gene UNIPROT PSEN1
gene UNIPROT TBC1D8
disease DOID Ad3
gene UNIPROT TRIM13
gene UNIPROT CXADR
gene UNIPROT CASR
gene UNIPROT NR1I3
gene UNIPROT PRKAR1A
gene UNIPROT SPG7
disease MESH multiple
gene UNIPROT CD46
disease DOID scid
drug DRUGBANK (S)-Des-Me-Ampa
gene UNIPROT ATN1
gene UNIPROT SNCA
gene UNIPROT NELFCD
gene UNIPROT SPATA2
pathway BSID Apoptosis
gene UNIPROT HMGB1
gene UNIPROT APCS
gene UNIPROT GNPTAB
disease MESH death
pathway BSID Reproduction
drug DRUGBANK Coenzyme M
disease DOID ovarian cancer
disease MESH sti
disease MESH ovarian cancer
disease MESH mesotheliomas
gene UNIPROT TNFRSF10B
gene UNIPROT SARS2
gene UNIPROT CDKN2A
gene UNIPROT MS4A2
gene UNIPROT PHF11
gene UNIPROT CD8A
gene UNIPROT NOG
gene UNIPROT LAMC2
gene UNIPROT CSF2
gene UNIPROT TNFAIP3
gene UNIPROT ARSA
drug DRUGBANK Acetylsalicylic acid
disease MESH metastasis
disease MESH weight loss
gene UNIPROT RAB8A
gene UNIPROT CD274
disease MESH tumors
gene UNIPROT TRAV38-2DV814q11.2
gene UNIPROT TBXT
disease DOID Ad5
drug DRUGBANK Sargramostim
disease DOID skin cancer
disease MESH skin cancer
pathway BSID Melanoma
disease DOID melanoma
disease MESH melanoma
gene UNIPROT PDCD1
drug DRUGBANK Pembrolizumab
gene UNIPROT RPL17

Original Article

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