Local Treatment of a Pediatric Osteosarcoma Model with a 4-1BBL Armed Oncolytic Adenovirus Results in an Antitumor Effect and Leads to Immune Memory

Martínez-Vélez, Naiara; Laspidea, Virginia; Labiano, Sara; García-Moure, Marc; Puigdelloses, Montse; Marrodán, Lucía; González-Huárriz, Marisol; Herrador, Guillermo; Nava, Daniel de la; Ausejo-Mauleon, Iker; Fueyo, Juan; Gomez-Manzano, Candelaria; Patiño-García, Ana; Zalacaín, Marta

doi:10.1158/1535-7163.mct-21-0565

Cited by 9 publications

(4 citation statements)

References 34 publications

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“…Currently, arming an oncolytic virus with immunomodulatory ligands can improve the antisarcoma effect of other oncolytic viruses. 41 , 42 There is a plethora of potential targets available to be used; however, human osteosarcoma samples express high levels of Gal3, 13 and its silencing in cultured human osteosarcoma cells was shown to decrease cell migration and invasion capabilities. 17 Importantly, Gal3 acts as a negative regulator of the innate and adaptive immune systems, thereby diminishing the immune response against the tumor, which underscores the potential of this protein as a therapeutic target.…”

Section: Discussionmentioning

confidence: 99%

Galectin-3 inhibition boosts the therapeutic efficacy of Semliki Forest virus in pediatric osteosarcoma

Herrador

Zalacaín

Labiano

et al. 2022

Molecular Therapy - Oncolytics

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Section: Discussionmentioning

confidence: 99%

Galectin-3 inhibition boosts the therapeutic efficacy of Semliki Forest virus in pediatric osteosarcoma

Herrador

Zalacaín

Labiano

et al. 2022

Molecular Therapy - Oncolytics

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“…In the quest to further improve the efficacy, our group engineered D24-ACT, which is based on the D24-RGD platform and armed with the immune costimulatory molecule 4-1BB ligand (4-1BBL), to improve the antitumor immune response. Local treatment with Delta-24-ACT in mice bearing orthotopic osteosarcoma murine tumors led to a reduction in both the primary tumor and metastases, and a significant increase in CD3+ and CD8+ T cells, among other immune populations, was found when comparing D24-ACT vs. D24-RGD ( 59 ). Our results suggest that potentiating the immune response could boost the efficacy in this type of tumor.…”

Section: Preclinical Studies Using Virotherapy In Pediatric Solid Tumorsmentioning

confidence: 99%

Immunovirotherapy for Pediatric Solid Tumors: A Promising Treatment That is Becoming a Reality

2022

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Immunotherapy has seen tremendous strides in the last decade, acquiring a prominent position at the forefront of cancer treatment since it has been proven to be efficacious for a wide variety of tumors. Nevertheless, while immunotherapy has changed the paradigm of adult tumor treatment, this progress has not yet been translated to the pediatric solid tumor population. For this reason, alternative curative therapies are urgently needed for the most aggressive pediatric tumors. In recent years, oncolytic virotherapy has consolidated as a feasible strategy for cancer treatment, not only for its tumor-specific effects and safety profile but also for its capacity to trigger an antitumor immune response. This review will summarize the current status of immunovirotherapy to treat cancer, focusing on pediatric solid malignancies. We will revisit previous basic, translational, and clinical research and discuss advances in overcoming the existing barriers and limitations to translate this promising therapeutic as an every-day cancer treatment for the pediatric and young adult populations.

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“…Current clinical treatment of osteosarcoma is mainly based on neoadjuvant chemotherapy followed by surgery plus postoperative radiotherapy and chemotherapy [4]. e past decades have witnessed the e ective improvement of osteosarcoma prognosis by using platinum chemotherapeutic agents such as cisplatin, which has improved 5-year survival rates for osteosarcoma to 60%-80% [11,12]. e main mechanism of cisplatin is the inhibition of proliferation of rapidly dividing cells through DNA damage [13,14].…”

Section: Introductionmentioning

confidence: 99%

Synthesis and Antitumor Activity of a GSH Inert Bisphosphonate Platinum (II) Complex

Liu

et al. 2022

Journal of Chemistry

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Osteosarcoma is a highly aggressive neoplasm. Traditional platinum chemotherapeutic agents for osteosarcoma inevitably have acquired drug resistance and serious side effects, which have limited their utility. To slow down the reaction of platinum drugs with glutathione (GSH) is a strategy to overcome the resistance of platinum chemotherapeutic agents. Herein, the unique design of a GSH inert bisphosphonate platinum complex cis-{di(amino)platinum[tetraethyl 2,2-bis(2-pyridinylmethyl)methylidene-1,1-bisphosphonate]} (DBPP) is reported. MTT assay demonstrates that DBPP showed moderate inhibition towards human osteosarcoma cell line U2OS cells. The cytostatic action of DBPP is related to conformational conversion from B-DNA to A-DNA and the unwinding of pUC19 DNA. DBPP could also destroy the tertiary structure of human serum albumin (HSA). Notably, 31P NMR and 1H NMR indicate that DBPP can hardly chelate with GSH, which could overcome the GSH-induced side effects. We envision that this unique design of the platinum complex would open up new ways to overcome GSH-induced resistance.

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Local Treatment of a Pediatric Osteosarcoma Model with a 4-1BBL Armed Oncolytic Adenovirus Results in an Antitumor Effect and Leads to Immune Memory

Abstract: Local treatment of a pediatric osteosarcoma model with a 4-1BBL armed oncolytic adenovirus results in an antitumor effect and leads to immune memory

Cited by 9 publications

References 34 publications

Galectin-3 inhibition boosts the therapeutic efficacy of Semliki Forest virus in pediatric osteosarcoma

Galectin-3 inhibition boosts the therapeutic efficacy of Semliki Forest virus in pediatric osteosarcoma

Immunovirotherapy for Pediatric Solid Tumors: A Promising Treatment That is Becoming a Reality

Synthesis and Antitumor Activity of a GSH Inert Bisphosphonate Platinum (II) Complex

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