Martí Farrera-Sal
TransgeneCytotoxicityGenetic enhancementFibroblast activation protein, alphaCD3CancerPeripheral blood mononuclear cellFunction (biology)Viral replicationGenomeAntigenClinical study designVirologyAntibodyTumor necrosis factor alphaLytic cycleChemistryMesenchymal stem cellIn vitroIn vivoVirusTranscriptional regulationT cellRetinoblastomaChemotherapyInflammationOncolytic adenovirusImmunotherapyImmunogenic cell deathHamsterCancer immunotherapyspliceMonocyteStem cellViral GenesCytokine secretionViral fitnessInsertion siteRecombinant DNAVirotherapyCancer researchStromaMedicineA549 cellCell cultureOncolytic virusBiologyCodon usage biasImmune systemCancer cell
10Publications
4H-index
95Citations
Publications 10
Newest
#1Martí Farrera-SalH-Index: 4
#2Rafael MorenoH-Index: 11
Last. Ramon AlemanyH-Index: 21
view all 6 authors...
Abstract null null Oncolytic viruses (OVs) preferentially infect and selectively replicate in cancer cells. OVs have been tested in clinical trials as monotherapy or in combination with chemotherapy, radiotherapy, and immunotherapy. However, the dense extracellular matrix hampers the intratumoral spreading and efficacy of OVs. Previously we described VCN-01, an oncolytic adenovirus expressing a soluble version of human sperm hyaluronidase PH20, which exhibited enhanced intratumoral distribution ...
Source
Source
Abstract Tumor targeting and intratumoral virus spreading are key features for successful oncolytic virotherapy. VCN-11 is a novel oncolytic adenovirus, genetically modified to express hyaluronidase (PH20) and display an albumin-binding domain (ABD) on the hexon. ABD allows the virus to self-coat with albumin when entering the bloodstream and evade neutralizing antibodies (NAbs). Here, we validate VCN-11 mechanism of action and characterize its toxicity. VCN-11 replication, hyaluronidase activit...
Source
#1Martí Farrera-SalH-Index: 4
#2Laura Moya-BorregoH-Index: 1
Last. Ramon AlemanyH-Index: 21
view all 4 authors...
Cancer immunotherapy targeting immune checkpoint inhibitors shows efficacy in several human cancers, but "cold tumors" that lack immune cells are typically unresponsive. Among the potential therapeutic approaches that could "heat" or promote lymphocyte infiltration of cold tumors, oncolytic viruses have attracted interest for their lytic and immunogenic mechanisms of action. Here we review the use of oncolytic adenoviruses in cancer immunotherapy, with a particular focus on pre-clinical and clin...
1 CitationsSource
Oncolytic adenoviruses (OAds) present limited efficacy in clinics. The insertion of therapeutic transgenes into OAds genomes, known as “arming OAds”, has been the main strategy to improve their therapeutic potential. Different approaches were published in the decade of the 2000s, but with few comparisons. Most armed OAds have complete or partial E3 deletions, leading to a shorter half-life in vivo. We generated E3+ OAds using two insertion sites, After-fiber and After-E4, and two different splic...
2 CitationsSource
#2Martí Farrera-SalH-Index: 4
Last. Cristina FillatH-Index: 31
view all 7 authors...
Arming oncolytic adenoviruses with therapeutic transgenes is a well-established strategy for multimodal tumour attack. However, this strategy sometimes leads to unexpected attenuated viral replication and a loss of oncolytic effects, preventing these viruses from reaching the clinic. Previous work has shown that altering codon usage in viral genes can hamper viral fitness. Here, we have analysed how transgene codon usage impacts viral replication and oncolytic activity. We observe that, although...
2 CitationsSource
#1Martí Farrera-SalH-Index: 4
#2Cristina Fillat (University of Barcelona)H-Index: 31
Last. Ramon AlemanyH-Index: 21
view all 3 authors...
Clinical results with oncolytic adenoviruses (OAds) used as antitumor monotherapies show limited efficacy. To increase OAd potency, transgenes have been inserted into their genome, a strategy known as “arming OAds”. Here, we review different parameters that affect the outcome of armed OAds. Recombinant adenovirus used in gene therapy and vaccination have been the basis for the design of armed OAds. Hence, early region 1 (E1) and early region 3 (E3) have been the most commonly used transgene inse...
5 CitationsSource
Background Oncolytic virus (OV)-based therapies have an emerging role in the treatment of solid tumors, involving both direct cell lysis and immunogenic cell death. Nonetheless, tumor-associated stroma limits the efficacy of oncolytic viruses by forming a barrier that blocks efficient viral penetration and spread. The stroma also plays a critical role in progression, immunosuppression and invasiveness of cancer. Fibroblast activation protein-α (FAP) is highly overexpressed in cancer-associated f...
53 CitationsSource
#1Guillem Pascual-Pasto (Hospital Sant Joan de Déu Barcelona)H-Index: 8
Last. Angel M. Carcaboso (Hospital Sant Joan de Déu Barcelona)H-Index: 27
view all 41 authors...
Retinoblastoma is a pediatric solid tumor of the retina activated upon homozygous inactivation of the tumor suppressor RB1 . VCN-01 is an oncolytic adenovirus designed to replicate selectively in tumor cells with high abundance of free E2F-1, a consequence of a dysfunctional RB1 pathway. Thus, we reasoned that VCN-01 could provide targeted therapeutic activity against even chemoresistant retinoblastoma. In vitro, VCN-01 effectively killed patient-derived retinoblastoma models. In mice, intravitr...
25 CitationsSource
#1Rafael MorenoH-Index: 11
Last. Ramon AlemanyH-Index: 21
view all 8 authors...
Several studies have evaluated the efficacy of using human oncolytic adenovirus-loaded mesenchymal stem cells for cancer treatment. For example, we have described the antitumor efficacy of CELYVIR, autologous bone marrow mesenchymal stem cells infected with the oncolytic adenovirus ICOVIR-5, for treatment of neuroblastoma patients. Results from this clinical trial point out the role of the immune system in the clinical outcome. In this context, a better understanding of the immunophenotypic chan...
17 CitationsSource