An Oncolytic Adenovirus Encoding SA-4-1BBL Adjuvant Fused to HPV-16 E7 Antigen Produces a Specific Antitumor Effect in a Cancer Mouse Model

Martinez-Perez, Alejandra G.; Perez‐Trujillo, José Juan; Garza-Morales, Rodolfo; Ramirez-Avila, Norma E.; Loera‐Arias, María de Jesús; Gómez-Gutiérrez, Jorge G.; Saucedo‐Cárdenas, Odila; García-García, Aracely; Rodríguez-Rocha, Humberto; Montes‐de‐Oca‐Luna, Roberto

doi:10.3390/vaccines9020149

Cited by 14 publications

(9 citation statements)

References 32 publications

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“…However, two recent studies using either an oncolytic adenovirus armed with 4-1BBL fused to the E7 antigen or a vaccinia Ankara virus armed with this same ligand showed the generation of immune memory in different tumor settings. 49 50 One plausible explanation is that Delta-24-ACT replication is markedly attenuated in murine cells due to species-specific adenoviral replication. 51 52 Therefore, in our model, we only observed a first wave of 4-1BBL expression, which might activate CD4+ and CD8+ T cells but be insufficient to sustain this activation or to costimulate new T cells that will be recruited into the tumor.…”

Section: Discussionmentioning

confidence: 99%

CD137 and PD-L1 targeting with immunovirotherapy induces a potent and durable antitumor immune response in glioblastoma models

Puigdelloses

García-Moure

Labiano

et al. 2021

J Immunother Cancer

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BackgroundGlioblastoma (GBM) is a devastating primary brain tumor with a highly immunosuppressive tumor microenvironment, and treatment with oncolytic viruses (OVs) has emerged as a promising strategy for these tumors. Our group constructed a new OV named Delta-24-ACT, which was based on the Delta-24-RGD platform armed with 4-1BB ligand (4-1BBL). In this study, we evaluated the antitumor effect of Delta-24-ACT alone or in combination with an immune checkpoint inhibitor (ICI) in preclinical models of glioma.MethodsThe in vitro effect of Delta-24-ACT was characterized through analyses of its infectivity, replication and cytotoxicity by flow cytometry, immunofluorescence (IF) and MTS assays, respectively. The antitumor effect and therapeutic mechanism were evaluated in vivo using several immunocompetent murine glioma models. The tumor microenvironment was studied by flow cytometry, immunohistochemistry and IF.ResultsDelta-24-ACT was able to infect and exert a cytotoxic effect on murine and human glioma cell lines. Moreover, Delta-24-ACT expressed functional 4-1BBL that was able to costimulate T lymphocytes in vitro and in vivo. Delta-24-ACT elicited a more potent antitumor effect in GBM murine models than Delta-24-RGD, as demonstrated by significant increases in median survival and the percentage of long-term survivors. Furthermore, Delta-24-ACT modulated the tumor microenvironment, which led to lymphocyte infiltration and alteration of their immune phenotype, as characterized by increases in the expression of Programmed Death 1 (PD-1) on T cells and Programmed Death-ligand 1 (PD-L1) on different myeloid cell populations. Because Delta-24-ACT did not induce an immune memory response in long-term survivors, as indicated by rechallenge experiments, we combined Delta-24-ACT with an anti-PD-L1 antibody. In GL261 tumor-bearing mice, this combination showed superior efficacy compared with either monotherapy. Specifically, this combination not only increased the median survival but also generated immune memory, which allowed long-term survival and thus tumor rejection on rechallenge.ConclusionsIn summary, our data demonstrated the efficacy of Delta-24-ACT combined with a PD-L1 inhibitor in murine glioma models. Moreover, the data underscore the potential to combine local immunovirotherapy with ICIs as an effective therapy for poorly infiltrated tumors.

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Section: Discussionmentioning

confidence: 99%

CD137 and PD-L1 targeting with immunovirotherapy induces a potent and durable antitumor immune response in glioblastoma models

Puigdelloses

García-Moure

Labiano

et al. 2021

J Immunother Cancer

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“…Immunization with a DNA vaccine encoding SP-SA-E7-4-1BBL in vivo showed an increase in antigenspecific interferon (IFN) levels associated with the therapeutic efficacy as Th1-mediated response to tumor eradication [43]. To improve the administration of SP-SA-E7-4-1BBL, we constructed an oncolytic adenovirus that encodes the previous construction and showed a specific antitumor effect in an established tumor mouse model [45].…”

Section: Sa-4-1bbl and Taasmentioning

confidence: 99%

“…Administration of OAd in mice with established TC-1 tumors resulted in tumor growth suppression and 100% survival when contrasted with the reference positive control. However, additional studies should analyze the safety and biodistribution of recombinant adenovirus and associate the mechanisms implicated in the antitumor effect [45].…”

Section: Oncolytic Virusmentioning

confidence: 99%

4-1BBL as a Mediator of Cross-Talk between Innate, Adaptive, and Regulatory Immunity against Cancer

Martinez-Perez

Perez‐Trujillo

Garza-Morales

et al. 2021

IJMS

Self Cite

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The ability of tumor cells to evade the immune system is one of the main challenges we confront in the fight against cancer. Multiple strategies have been developed to counteract this situation, including the use of immunostimulant molecules that play a key role in the anti-tumor immune response. Such a response needs to be tumor-specific to cause as little damage as possible to healthy cells and also to track and eliminate disseminated tumor cells. Therefore, the combination of immunostimulant molecules and tumor-associated antigens has been implemented as an anti-tumor therapy strategy to eliminate the main obstacles confronted in conventional therapies. The immunostimulant 4-1BBL belongs to the tumor necrosis factor (TNF) family and it has been widely reported as the most effective member for activating lymphocytes. Hence, we will review the molecular, pre-clinical, and clinical applications in conjunction with tumor-associated antigens in antitumor immunotherapy, as well as the main molecular pathways involved in this association.

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“…OVs can promote the anti-tumor immune response by inducing tumor cell immunogenic cell death [ 102 ]. During the oncolytic process of the virus on tumor cells, it releases tumor-associated antigens (TAAs) and produces inflammatory cytokines [ 103 ]. The result is that OVs can transform the immunosuppressive “cold” tumor microenvironment into a “hot” immune stimulation environment.…”

Section: Preclinical Studies Of Ovsmentioning

confidence: 99%

Oncolytic viral vectors in the era of diversified cancer therapy: from preclinical to clinical

Tang

et al. 2022

Clin Transl Oncol

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With the in-depth research and wide application of immunotherapy recently, new therapies based on oncolytic viruses are expected to create new prospects for cancer treatment via eliminating the suppression of the immune system by tumors. Currently, an increasing number of viruses are developed and engineered, and various virus vectors based on effectively stimulating human immune system to kill tumor cells have been approved for clinical treatment. Although the virus can retard the proliferation of tumor cells, the choice of oncolytic viruses in biological cancer therapy is equally critical given their therapeutic efficacy, safety and adverse effects. Moreover, previously known oncolytic viruses have not been systematically classified. Therefore, in this review, we summarized and distinguished the characteristics of several common types of oncolytic viruses: herpes simplex virus, adenovirus, measles virus, Newcastle disease virus, reovirus and respiratory syncytial virus. Subsequently, we outlined that these oncolytic viral vectors have been transformed from preclinical studies in combination with immunotherapy, radiotherapy, chemotherapy, and nanoparticles into clinical therapeutic strategies for various advanced solid malignancies or circulatory system cancers.

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An Oncolytic Adenovirus Encoding SA-4-1BBL Adjuvant Fused to HPV-16 E7 Antigen Produces a Specific Antitumor Effect in a Cancer Mouse Model

Cited by 14 publications

References 32 publications

CD137 and PD-L1 targeting with immunovirotherapy induces a potent and durable antitumor immune response in glioblastoma models

CD137 and PD-L1 targeting with immunovirotherapy induces a potent and durable antitumor immune response in glioblastoma models

4-1BBL as a Mediator of Cross-Talk between Innate, Adaptive, and Regulatory Immunity against Cancer

Oncolytic viral vectors in the era of diversified cancer therapy: from preclinical to clinical

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