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|Ref Type||Journal Article|
|Authors||Aznar MA, Planelles L, Perez-Olivares M, Molina C, Garasa S, Etxeberría I, Perez G, Rodriguez I, Bolaños E, Lopez-Casas P, Rodriguez-Ruiz ME, Perez-Gracia JL, Marquez-Rodas I, Teijeira A, Quintero M, Melero I|
|Title||Immunotherapeutic effects of intratumoral nanoplexed poly I:C.|
|Journal||Journal for immunotherapy of cancer|
|Date||2019 05 02|
|Abstract Text||Poly I:C is a powerful immune adjuvant as a result of its agonist activities on TLR-3, MDA5 and RIG-I. BO-112 is a nanoplexed formulation of Poly I:C complexed with polyethylenimine that causes tumor cell apoptosis showing immunogenic cell death features and which upon intratumoral release results in more prominent tumor infiltration by T lymphocytes. Intratumoral treatment with BO-112 of subcutaneous tumors derived from MC38, 4 T1 and B16-F10 leads to remarkable local disease control dependent on type-1 interferon and gamma-interferon. Some degree of control of non-injected tumor lesions following BO-112 intratumoral treatment was found in mice bearing bilateral B16-OVA melanomas, an activity which was enhanced with co-treatment with systemic anti-CD137 and anti-PD-L1 mAbs. More abundant CD8+ T lymphocytes were found in B16-OVA tumor-draining lymph nodes and in the tumor microenvironment following intratumoral BO-112 treatment, with enhanced numbers of tumor antigen-specific cytotoxic T lymphocytes. Genome-wide transcriptome analyses of injected tumor lesions were consistent with a marked upregulation of the type-I interferon pathway. Inspired by these data, intratumorally delivered BO-112 is being tested in cancer patients (NCT02828098).|
|Molecular Profile||Treatment Approach|
|Gene Name||Source||Synonyms||Protein Domains||Gene Description||Gene Role|
|Therapy Name||Drugs||Efficacy Evidence||Clinical Trials|
|Drug Name||Trade Name||Synonyms||Drug Classes||Drug Description|
|BO-112||BO 112|BO112||BO-112 is a nanoparticle formulation of a synthetic double stranded RNA (poly I:C) complex, which potentially enhances anti-tumor immune response, induces apoptosis, and decreases tumor growth (PMID: 31046839).|
|Gene||Variant||Impact||Protein Effect||Variant Description||Associated with drug Resistance|
|Molecular Profile||Indication/Tumor Type||Response Type||Therapy Name||Approval Status||Evidence Type||Efficacy Evidence||References|
|Unknown unknown||melanoma||not applicable||BO-112||Preclinical - Patient cell culture||Actionable||In a preclinical study, BO-112 treatment inhibited cell viability and induced apoptosis in mouse melanoma cells, and induced cytotoxicity and increased apoptosis in cells derived from metastatic lesions of melanoma patients in culture, and intratumoral delivery of BO-112 enhanced infiltration of T-lymphocytes, reduced tumor growth, and delayed progression in syngeneic mouse models (PMID: 31046839).||31046839|
|Unknown unknown||breast cancer||not applicable||BO-112||Preclinical - Cell culture||Actionable||In a preclinical study, BO-112 treatment induced cytotoxicity in human breast cancer cell lines and inhibited viability of mouse triple-negative breast cancer (TNBC) cells in culture, and intratumoral delivery of BO-112 reduced tumor growth in a syngeneic mouse model of TNBC (PMID: 31046839).||31046839|
|Unknown unknown||colon cancer||not applicable||BO-112||Preclinical - Cell culture||Actionable||In a preclinical study, BO-112 treatment inhibited viability of mouse colon carcinoma cells, and reduced cell viability, and induced cytotoxicity and apoptosis in human colon cancer cell lines in culture, and intratumoral delivery of BO-112 reduced tumor growth in a syngeneic mouse model of colon carcinoma (PMID: 31046839).||31046839|