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Sci Rep
2022 Aug 10;121:13636. doi: 10.1038/s41598-022-17775-y.
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Potentiation of combined p19Arf and interferon-beta cancer gene therapy through its association with doxorubicin chemotherapy.
Medrano RFV
,
Salles TA
,
Dariolli R
,
Antunes F
,
Feitosa VA
,
Hunger A
,
Catani JPP
,
Mendonça SA
,
Tamura RE
,
Lana MG
,
Rodrigues EG
,
Strauss BE
.
Abstract
Balancing safety and efficacy is a major consideration for cancer treatments, especially when combining cancer immunotherapy with other treatment modalities such as chemotherapy. Approaches that induce immunogenic cell death (ICD) are expected to eliminate cancer cells by direct cell killing as well as activation of an antitumor immune response. We have developed a gene therapy approach based on p19Arf and interferon-β gene transfer that, similar to conventional inducers of ICD, results in the release of DAMPS and immune activation. Here, aiming to potentiate this response, we explore whether association between our approach and treatment with doxorubicin (Dox), a known inducer of ICD, could further potentiate treatment efficacy without inducing cardiotoxicity, a critical side effect of Dox. Using central composite rotational design analysis, we show that cooperation between gene transfer and chemotherapy killed MCA205 and B16F10 cells and permitted the application of reduced viral and drug doses. The treatments also cooperated to induce elevated levels of ICD markers in MCA205, which correlated with improved efficacy of immunotherapy in vivo. Treatment of subcutaneous MCA205 tumors associating gene transfer and low dose (10 mg/kg) chemotherapy resulted in inhibition of tumor progression. Moreover, the reduced dose did not cause cardiotoxicity as compared to the therapeutic dose of Dox (20 mg/kg). The association of p19Arf/interferon-β gene transfer and Dox chemotherapy potentiated antitumor response and minimized cardiotoxicity.
Angsutararux,
Chemotherapy-Induced Cardiotoxicity: Overview of the Roles of Oxidative Stress.
2015, Pubmed
Angsutararux,
Chemotherapy-Induced Cardiotoxicity: Overview of the Roles of Oxidative Stress.
2015,
Pubmed
Apetoh,
Toll-like receptor 4-dependent contribution of the immune system to anticancer chemotherapy and radiotherapy.
2007,
Pubmed
Arlen,
Combining Vaccines with Conventional Therapies for Cancer.
2007,
Pubmed
Asano,
CD169-positive macrophages dominate antitumor immunity by crosspresenting dead cell-associated antigens.
2011,
Pubmed
Bajgelman,
AAVPG: a vigilant vector where transgene expression is induced by p53.
2013,
Pubmed
Casares,
Caspase-dependent immunogenicity of doxorubicin-induced tumor cell death.
2005,
Pubmed
Catani,
Intratumoral Immunization by p19Arf and Interferon-β Gene Transfer in a Heterotopic Mouse Model of Lung Carcinoma.
2016,
Pubmed
Corrales,
The host STING pathway at the interface of cancer and immunity.
2016,
Pubmed
Ding,
Chemotherapy rescues tumor-driven aberrant CD4+ T-cell differentiation and restores an activated polyfunctional helper phenotype.
2010,
Pubmed
Fridlender,
Chemotherapy delivered after viral immunogene therapy augments antitumor efficacy via multiple immune-mediated mechanisms.
2010,
Pubmed
Galluzzi,
Consensus guidelines for the definition, detection and interpretation of immunogenic cell death.
2020,
Pubmed
Galluzzi,
Immunogenic cell death in cancer and infectious disease.
2017,
Pubmed
Galluzzi,
Molecular definitions of cell death subroutines: recommendations of the Nomenclature Committee on Cell Death 2012.
2012,
Pubmed
Garg,
Hypericin-based photodynamic therapy induces surface exposure of damage-associated molecular patterns like HSP70 and calreticulin.
2012,
Pubmed
Huang,
Caspase 3-mediated stimulation of tumor cell repopulation during cancer radiotherapy.
2011,
Pubmed
Hunger,
Reestablishment of p53/Arf and interferon-β pathways mediated by a novel adenoviral vector potentiates antiviral response and immunogenic cell death.
2017,
Pubmed
Kaneno,
Chemomodulation of human dendritic cell function by antineoplastic agents in low noncytotoxic concentrations.
2009,
Pubmed
Kroemer,
Immunogenic cell death in cancer therapy.
2013,
Pubmed
Lang,
Recommendations for chamber quantification: a report from the American Society of Echocardiography's Guidelines and Standards Committee and the Chamber Quantification Writing Group, developed in conjunction with the European Association of Echocardiography, a branch of the European Society of Cardiology.
2005,
Pubmed
Lavin,
Innate Immune Landscape in Early Lung Adenocarcinoma by Paired Single-Cell Analyses.
2017,
Pubmed
Le,
Gemcitabine directly inhibits myeloid derived suppressor cells in BALB/c mice bearing 4T1 mammary carcinoma and augments expansion of T cells from tumor-bearing mice.
2009,
Pubmed
Ma,
Contribution of IL-17-producing gamma delta T cells to the efficacy of anticancer chemotherapy.
2011,
Pubmed
Ma,
Tumor necrosis factor is dispensable for the success of immunogenic anticancer chemotherapy.
2013,
Pubmed
Ma,
Anticancer chemotherapy-induced intratumoral recruitment and differentiation of antigen-presenting cells.
2013,
Pubmed
Martins,
Restoration of the immunogenicity of cisplatin-induced cancer cell death by endoplasmic reticulum stress.
2011,
Pubmed
Medrano,
Uncovering the immunotherapeutic cycle initiated by p19Arf and interferon-β gene transfer to cancer cells: An inducer of immunogenic cell death.
2017,
Pubmed
Medrano,
Vaccination using melanoma cells treated with p19arf and interferon beta gene transfer in a mouse model: a novel combination for cancer immunotherapy.
2016,
Pubmed
Melero,
Evolving synergistic combinations of targeted immunotherapies to combat cancer.
2015,
Pubmed
Merkel,
Combined p19Arf and interferon-beta gene transfer enhances cell death of B16 melanoma in vitro and in vivo.
2013,
Pubmed
Merkel,
Activation of endogenous p53 by combined p19Arf gene transfer and nutlin-3 drug treatment modalities in the murine cell lines B16 and C6.
2010,
Pubmed
Michaud,
Autophagy-dependent anticancer immune responses induced by chemotherapeutic agents in mice.
2011,
Pubmed
Obeid,
Calreticulin exposure dictates the immunogenicity of cancer cell death.
2007,
Pubmed
Octavia,
Doxorubicin-induced cardiomyopathy: from molecular mechanisms to therapeutic strategies.
2012,
Pubmed
Ravishankar,
Marginal zone CD169+ macrophages coordinate apoptotic cell-driven cellular recruitment and tolerance.
2014,
Pubmed
Spranger,
Tumor-Residing Batf3 Dendritic Cells Are Required for Effector T Cell Trafficking and Adoptive T Cell Therapy.
2017,
Pubmed
Tamura,
Autoregulated expression of p53 from an adenoviral vector confers superior tumor inhibition in a model of prostate carcinoma gene therapy.
2016,
Pubmed
Thorn,
Doxorubicin pathways: pharmacodynamics and adverse effects.
2011,
Pubmed
Vacchelli,
Chemotherapy-induced antitumor immunity requires formyl peptide receptor 1.
2015,
Pubmed
Viaud,
The intestinal microbiota modulates the anticancer immune effects of cyclophosphamide.
2013,
Pubmed
Vilain,
Dynamic Changes in PD-L1 Expression and Immune Infiltrates Early During Treatment Predict Response to PD-1 Blockade in Melanoma.
2017,
Pubmed
Wen,
A systematic analysis of experimental immunotherapies on tumors differing in size and duration of growth.
2012,
Pubmed
Xu,
Intratumoral Delivery of IL-21 Overcomes Anti-Her2/Neu Resistance through Shifting Tumor-Associated Macrophages from M2 to M1 Phenotype.
2015,
Pubmed
Zhang,
Differential impairment of regulatory T cells rather than effector T cells by paclitaxel-based chemotherapy.
2008,
Pubmed
