Aptamer targeted therapy potentiates immune checkpoint blockade in triple-negative breast cancer (149 views) (PDF public 60 views)
J Exp Clin Canc Res (ISSN: 0392-9078linking, 1756-9966, 1756-9966electronic), 2020 Sep 7; 39(1): 180-180.
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Paper type: Journal Article,
Impact factor: 7.068, 5-year impact factor: 5.28
Url: Not available.
Keywords: Antitumor Immunity , Aptamer , Metastases , Pd-L1 Monoclonal Antibody , Pdgfrβ , Tnbc , Tumor Microenvironment,
Affiliations:
*** IBB - CNR ***
Institute of Experimental Endocrinology and Oncology "Gaetano Salvatore", CNR, Via S. Pansini 5, 80131, Naples, Italy.
Department of Molecular Medicine and Medical Biotechnology, University of Naples "Federico II", Via Pansini 5, 80131, Naples, Italy.
Ceinge-Biotecnologie Avanzate s.c.a.r.l., via Gaetano Salvatore 486, 80145, Naples, Italy.
Pathology Unit, Istituto Nazionale Tumori-IRCCS-Fondazione G. Pascale, Naples, Italy.
Group of Experimental Biotherapy and Diagnostic, Institute for Regenerative Medicine, Sechenov First Moscow State Medical University, Moscow, 119991, Russia.
Institute of Biostructure and Bioimaging, CNR, Via T. De Amicis 95, 80145, Naples, Italy.
References:
Not available.
J Exp Clin Canc Res (ISSN: 0392-9078linking, 1756-9966, 1756-9966electronic), 2020 Sep 7; 39(1): 180-180.
Export to BibTeX Export to EndNote
Paper type: Journal Article,
Impact factor: 7.068, 5-year impact factor: 5.28
Url: Not available.
Keywords: Antitumor Immunity , Aptamer , Metastases , Pd-L1 Monoclonal Antibody , Pdgfrβ , Tnbc , Tumor Microenvironment,
Affiliations:
*** IBB - CNR ***
Institute of Experimental Endocrinology and Oncology "Gaetano Salvatore", CNR, Via S. Pansini 5, 80131, Naples, Italy.
Department of Molecular Medicine and Medical Biotechnology, University of Naples "Federico II", Via Pansini 5, 80131, Naples, Italy.
Ceinge-Biotecnologie Avanzate s.c.a.r.l., via Gaetano Salvatore 486, 80145, Naples, Italy.
Pathology Unit, Istituto Nazionale Tumori-IRCCS-Fondazione G. Pascale, Naples, Italy.
Group of Experimental Biotherapy and Diagnostic, Institute for Regenerative Medicine, Sechenov First Moscow State Medical University, Moscow, 119991, Russia.
Institute of Biostructure and Bioimaging, CNR, Via T. De Amicis 95, 80145, Naples, Italy.
References:
Not available.
Aptamer targeted therapy potentiates immune checkpoint blockade in triple-negative breast cancer
BACKGROUND: Triple-negative breast cancer (TNBC) is a uniquely aggressive cancer with high rates of relapse due to resistance to chemotherapy. TNBC expresses higher levels of programmed cell death-ligand 1 (PD-L1) compared to other breast cancers, providing the rationale for the recently approved immunotherapy with anti-PD-L1 monoclonal antibodies (mAbs). A huge effort is dedicated to identify actionable biomarkers allowing for combination therapies with immune-checkpoint blockade. Platelet-derived growth factor receptor β (PDGFRβ) is highly expressed in invasive TNBC, both on tumor cells and tumor microenvironment. We recently proved that tumor growth and lung metastases are impaired in mouse models of human TNBC by a high efficacious PDGFRβ aptamer. Hence, we aimed at investigating the effectiveness of a novel combination treatment with the PDGFRβ aptamer and anti-PD-L1 mAbs in TNBC. METHODS: The targeting ability of the anti-human PDGFRβ aptamer toward the murine receptor was verified by streptavidin-biotin assays and confocal microscopy, and its inhibitory function by transwell migration assays. The anti-proliferative effects of the PDGFRβ aptamer/anti-PD-L1 mAbs combination was assessed in human MDA-MB-231 and murine 4 T1 TNBC cells, both grown as monolayer or co-cultured with lymphocytes. Tumor cell lysis and cytokines secretion by lymphocytes were analyzed by LDH quantification and ELISA, respectively. Orthotopic 4 T1 xenografts in syngeneic mice were used for dissecting the effect of aptamer/mAb combination on tumor growth, metastasis and lymphocytes infiltration. Ex vivo analyses through immunohistochemistry, RT-qPCR and immunoblotting were performed. RESULTS: We show that the PDGFRβ aptamer potentiates the anti-proliferative activity of anti-PD-L1 mAbs on both human and murine TNBC cells, according to its human/mouse cross-reactivity. Further, by binding to activated human and mouse lymphocytes, the aptamer enhances the anti-PD-L1 mAb-induced cytotoxicity of lymphocytes against tumor cells. Importantly, the aptamer heightens the antibody efficacy in inhibiting tumor growth and lung metastases in mice. It acts on both tumor cells, inhibiting Akt and ERK1/2 signaling pathways, and immune populations, increasing intratumoral CD8 + T cells and reducing FOXP3 + Treg cells. CONCLUSION: Co-treatment of PDGFRβ aptamer with anti-PD-L1 mAbs is a viable strategy, thus providing for the first time an evidence of the efficacy of PDGFRβ/PD-L1 co-targeting combination therapy in TNBC.
BACKGROUND: Triple-negative breast cancer (TNBC) is a uniquely aggressive cancer with high rates of relapse due to resistance to chemotherapy. TNBC expresses higher levels of programmed cell death-ligand 1 (PD-L1) compared to other breast cancers, providing the rationale for the recently approved immunotherapy with anti-PD-L1 monoclonal antibodies (mAbs). A huge effort is dedicated to identify actionable biomarkers allowing for combination therapies with immune-checkpoint blockade. Platelet-derived growth factor receptor β (PDGFRβ) is highly expressed in invasive TNBC, both on tumor cells and tumor microenvironment. We recently proved that tumor growth and lung metastases are impaired in mouse models of human TNBC by a high efficacious PDGFRβ aptamer. Hence, we aimed at investigating the effectiveness of a novel combination treatment with the PDGFRβ aptamer and anti-PD-L1 mAbs in TNBC. METHODS: The targeting ability of the anti-human PDGFRβ aptamer toward the murine receptor was verified by streptavidin-biotin assays and confocal microscopy, and its inhibitory function by transwell migration assays. The anti-proliferative effects of the PDGFRβ aptamer/anti-PD-L1 mAbs combination was assessed in human MDA-MB-231 and murine 4 T1 TNBC cells, both grown as monolayer or co-cultured with lymphocytes. Tumor cell lysis and cytokines secretion by lymphocytes were analyzed by LDH quantification and ELISA, respectively. Orthotopic 4 T1 xenografts in syngeneic mice were used for dissecting the effect of aptamer/mAb combination on tumor growth, metastasis and lymphocytes infiltration. Ex vivo analyses through immunohistochemistry, RT-qPCR and immunoblotting were performed. RESULTS: We show that the PDGFRβ aptamer potentiates the anti-proliferative activity of anti-PD-L1 mAbs on both human and murine TNBC cells, according to its human/mouse cross-reactivity. Further, by binding to activated human and mouse lymphocytes, the aptamer enhances the anti-PD-L1 mAb-induced cytotoxicity of lymphocytes against tumor cells. Importantly, the aptamer heightens the antibody efficacy in inhibiting tumor growth and lung metastases in mice. It acts on both tumor cells, inhibiting Akt and ERK1/2 signaling pathways, and immune populations, increasing intratumoral CD8 + T cells and reducing FOXP3 + Treg cells. CONCLUSION: Co-treatment of PDGFRβ aptamer with anti-PD-L1 mAbs is a viable strategy, thus providing for the first time an evidence of the efficacy of PDGFRβ/PD-L1 co-targeting combination therapy in TNBC.
Aptamer targeted therapy potentiates immune checkpoint blockade in triple-negative breast cancer
| ▼ Molecular imaging for personalized therapy in oncology |
| ▼ Imaging Tumor Acidosis |
Aptamer targeted therapy potentiates immune checkpoint blockade in triple-negative breast cancer
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Impact Factor: 8.29
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Mazziotti G, Formenti AM, Panarotto MB, Arvat E, Chiti A, Cuocolo A, Dottorini ME, Durante C, Agate L, Filetti S, Felicetti F, Filice A, Pace L, Pellegrino T, Rodari M, Salvatori M, Tranfaglia C, Versari A, Viola D, Frara S, Berruti A, Giustina A, Giubbini R
* Real-life management and outcome of thyroid carcinoma-related bone metastases: results from a nationwide multicenter experience (511 views)
Endocrine (ISSN: 1355-008x, 1355-008xlinking), 2017 Nov 06; 59(1): 90-101.
Impact Factor: 3.179
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Hill BS, Pelagalli A, Passaro N, Zannetti A
* Tumor-educated mesenchymal stem cells promote pro-metastatic phenotype (348 views)
Oncotarget (ISSN: 1949-2553electronic, 1949-2553linking), 2017 Sep 22; 8(42): 73296-73311.
Impact Factor: 5.168
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Camorani S, Hill BS, Fontanella R, Greco A, Gramanzini M, Auletta L, Gargiulo S, Albanese S, Lucarelli E, Cerchia L, Zannetti A
* Inhibition of Bone Marrow-Derived Mesenchymal Stem Cells Homing Towards Triple-Negative Breast Cancer Microenvironment Using an Anti-PDGFRbeta Aptamer (780 views) (PDF 228 views)
Theranostics (ISSN: 1838-7640, 1838-7640electronic), 2017 Aug 22; 7(14): 3595-3607.
Impact Factor: 8.537
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Longo DL, Stefania R, Aime S, Oraevsky A
* Melanin-Based Contrast Agents for Biomedical Optoacoustic Imaging and Theranostic Applications (704 views)
Int J Mol Sc (ISSN: 1422-0067, 1661-6596, 1422-0067linking), 2017 Aug 7; 18(8): N/D-N/D.
Impact Factor: 3.687
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Sapuppo G, Palermo F, Russo M, Tavarelli M, Masucci R, Squatrito S, Vigneri R, Pellegriti G
* Latero-cervical lymph node metastases (N1b) represent an additional risk factor for papillary thyroid cancer outcome (263 views)
J Endocrinol Invest (ISSN: 1720-8386, 0391-4097, 1720-8386electronic), 2017 Jun 23; N/D: N/D-N/D.
Impact Factor: 3.166
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Mainenti PP, Romano F, Pizzuti L, Segreto S, Storto G, Mannelli L, Imbriaco M, Camera L, Maurea S
* Non-invasive diagnostic imaging of colorectal liver metastases (289 views)
World J Radiol (ISSN: 1949-8470electronic, 1949-8470linking), 2015 Jul 28; 7(7): 157-169.
Impact Factor: 0.567
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Gallicchio R, Giacomobono S, Nardelli A, Pellegrino T, Simeon V, Gattozzi D, Maddalena F, Mainenti PP, Storto G
* Palliative Treatment Of Bone Metastases With Samarium-153 Edtmp At Onset Of Pain (496 views)
J Bone Miner Metab (ISSN: 0914-8779), 2014 Jul; 32(4): 434-440.
Impact Factor: 2.46
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Perri F, Dell'Oca I, Muto P, Schiavone C, Aversa C, Fulciniti F, Solla R, Scarpati GD, Buonerba C, Di Lorenzo G, Caponigro F
* Optimal management of a patient with recurrent nasopharyngeal carcinoma (342 views)
World Journal Of Clinical Cases (ISSN: 2307-8960), 2014; 2(7): 297-300.
Impact Factor: 0.895
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D'Antuono F, Nardelli A, Gallicchio R, Giacomobono S, Venetucci A, Pellegrino T, Leggiadro F, D'Errico N, Gattozzi D, Mainenti PP, Storto G
* Palliative Treatment of Bone Metastases with Sm-153 EDTMP at Pain Onset (343 views)
Eur J Nucl Med (ISSN: 1619-7070, 1619-7089, 0340-6997), 2013 Oct; 40: N/D-N/D.
Impact Factor: 5.217
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Portella L, Vitale R, De Luca S, D'Alterio C, Ieranò C, Napolitano M, Riccio A, Polimeno MN, Monfregola L, Barbieri A, Luciano A, Ciarmiello A, Arra C, Castello G, Amodeo P, Scala S
* Preclinical Development of a Novel Class of CXCR4 Antagonist Impairing Solid Tumors Growth and Metastases (579 views)
Plosone (ISSN: 1932-6203, 1932-6203electronic, 1932-6203linking), 2013 Sep 13; 8(9): N/D-N/D.
Impact Factor: 3.534
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Storto G, Gallicchio R, Pellegrino T, Nardelli A, Capacchione D, Sirignano C, Pace L
* Impact of F-18-fluoride PET-CT on implementing early treatment of painful bone metastases with Sm-153 EDTMP (457 views) (PDF 32 views)
Nucl Med Biol (ISSN: 0969-8051, 0883-2897, 0969-8051linking), 2013 May; 40(4): 518-523.
Impact Factor: 2.408
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Gringeri CV, Menchise V, Rizzitelli S, Cittadino E, Catanzaro V, Dati G, Chaabane L, Digilio G, Aime S
* Novel Gd(III)-based probes for MR molecular imaging of matrix metalloproteinases (605 views)
Contrast Media Mol Imaging (ISSN: 1555-4309, 1555-4309linking), 2012 Mar; 7(2): 175-184.
Impact Factor: 2.872
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Mainenti PP, Mancini M, Mainolfi C, Camera L, Maurea S, Manchia A, Tanga M, Persico F, Addeo P, D'Antonio D, Speranza A, Bucci L, Persico G, Pace L, Salvatore M
* Detection of colo-rectal liver metastases: Prospective comparison of contrast enhanced US, multidetector CT, PET/CT, and 1. 5 Tesla MR with extracellular and reticulo-endothelial cell specific contrast agents (628 views)
Abdom Imaging (ISSN: 0942-8925, 1432-0509), 2010 Oct; 35(5): 511-521.
Impact Factor: 1.95
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Palmieri C, Falcone C, Iaccino E, Tuccillo FM, Gaspari M, Trimboli F, De Laurentiis A, Luberto L, Pontoriero M, Pisano A, Vecchio E, Fierro O, Panico M, Larobina M, Gargiulo S, Costa N, Dal Piaz F, Schiavone M, Arra C, Giudice A, Palma G, Barbieri A, Quinto I, Scala G
* In vivo targeting and growth inhibition of the A20 murine B-cell lymphoma by an idiotype-specific peptide binder (763 views)
Blood (ISSN: 0006-4971, 0006-6497, 0390-6078), 2010 Jul 15; 116(2): 226-238.
Impact Factor: 10.558
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Del Vecchio S, Zannetti A, Iommelli F, Lettieri A, Brunetti A, Salvatore M
* Molecular imaging of tumor microenvironment (776 views)
Q J Nucl Med Mol Im (ISSN: 1824-4785, 1824-4478, 1824-4785linking), 2010 Jun; 54(3): 243-258.
Impact Factor: 1.724
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Del Vecchio S, Zannetti A, Iommelli F, Lettieri A, Brunetti A, Salvatore M
* Molecular imaging of tumor microenvironment: Challenges and perspectives (694 views)
Q J Nucl Med Mol Im (ISSN: 1824-4785, 1824-4478, 1824-4785linking), 2010 Jun; 54(3): 249-258.
Impact Factor: 1.724
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Zollo M, Marino N, Garzia L, Cusanelli E, Maffia V, Virgilio A, Navas L, Taglialatela A, De Martino D, Terracciano L, Tornillo L, Gargiulo S, Brunetti A, Galeone A
* h-Prune, a target for therapeutic intervention to fight cancer metastases (306 views)
Clinical & Experimental Metastasis (ISSN: 0262-0898), 2009 Oct; 26(7): N/D-N/D.
Impact Factor: 3.91
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Storto G, Pellegrino T, Nardelli A, De Falco T, Castaldi E, Ortosecco G, Capasso E, Erra P, Speranza A, Klain M, Molino L, Di Nuzzo C, Pace L, Salvatore M
* Impact of PET-CT with F-18 Fluoride in Implementing Treatment of Painful Bone Metastases with Sm-153 EDTMP (320 views)
Eur J Nucl Med (ISSN: 1619-7070, 1619-7089, 0340-6997), 2008 Oct; 35: N/D-N/D.
Impact Factor: 4.532
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Mainenti PP, Mainolfi C, Storto G, Salvatore B, Nardelli A, De Marino M, Caliendo A, Nappi R, Pace L, Salvatore M
* Detection of liver Metastases in patients with colorectal carcinoma: Comparison of multidetector-CT, Mr, ultrasound and PET-CT (445 views)
Eur J Nucl Med (ISSN: 1619-7070, 1619-7089, 0340-6997), 2007 Oct; 34: N/D-N/D.
Impact Factor: 4.101
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Storto G, Klain M, Paone G, Liuzzi R, Molino L, Marinelli A, Soricelli A, Pace L, Salvatore M
* Combined therapy of Sr-89 and zoledronic acid in patients with painful bone metastases (518 views)
Bone (ISSN: 8756-3282), 2006 Jul; 39(1): 35-41.
Impact Factor: 3.829
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Storto G, Paone G, Klain M, Salvatore B, Capacchione D, Soricelli A, Pace L, Salvatore M
* Hematological Toxicity in Patients with Painful Bone Metastases Treated with Sr-89 and Zoledronic Acid (313 views)
Eur J Nucl Med (ISSN: 1619-7070, 1619-7089, 0340-6997), 2005 Sep; 32: N/D-N/D.
Impact Factor: 3.883
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Storto G, Paone G, Ibello F, Klain M, Liuzzi R, Marinelli A, Soricelli A, Pace L, Salvatore M
* Combined therapy of Sr-89 and zoledronic acid in patients with painful bone metastases (406 views)
Eur J Nucl Med (ISSN: 1619-7070, 1619-7089, 0340-6997), 2004 Sep; 31: N/D-N/D.
Impact Factor: 3.935
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Sijens PE, Knopp MV, Brunetti A, Wicklow K, Alfano B, Bachert P, Sanders JA, Stillman AE, Kett H, Sauter R
1H MR spectroscopy in patients with metastatic brain tumors: A multicenter study (408 views)
Magn Reson Med (ISSN: 0740-3194, 1522-2594electronic, 0740-3194linking), 1995 Jun; 33(6): 818-826.
Impact Factor: 3.012
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35 Records (27 excluding Abstracts).
Total impact factor: 159.228 (127.708 excluding Abstracts).
Total 5 year impact factor: 109.782 (77.022 excluding Abstracts).
Total impact factor: 159.228 (127.708 excluding Abstracts).
Total 5 year impact factor: 109.782 (77.022 excluding Abstracts).
149 views. Last view on Wednesday 25 September 2024, 13:31:57
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