Novel Human Bispecific Aptamer–Antibody Conjugates for Efficient Cancer Cell Killing
Abstract
:1. Introduction
2. Results
2.1. Evaluation of the Effects on Tumor Cells of Combined Treatments of Erb-hcAb with Anti-EGFR Aptamer
2.2. Evaluation of the Effects on Tumor Cell Viability of Combined Treatments of Anti-PD-L1 mAb with Anti-EGFR Aptamer
2.3. Construction and Purification of the New Bispecific Constructs Made up of Erb-hcAb or 10_12 mAb Conjugated with the Anti-EGFR Aptamer
2.4. Characterization of Antibody–Aptamer Conjugates
2.5. Cytotoxic Effects of the Novel Aptamer–Antibody Conjugates on Tumor Cells
3. Discussion
- (1)
- Easy and quick procedures for production;
- (2)
- Low cost of production;
- (3)
- Simultaneous inhibition of two targets with enhanced antitumor effects;
- (4)
- Increased specificity, due to the simultaneous targeting of two different antigens, for tumor cells that express both antigens, thus limiting unwanted side effects on normal cells expressing only one of the antigens; and
- (5)
- Potential increased pharmacokinetic and pharmacodynamic properties due to the combination of the advantages of small size aptamer for increasing tumor penetration and target accessibility with those of the antibody, which allows for less rapid clearance by renal filtration and longer half-life in circulation.
4. Materials and Methods
4.1. Cell Cultures
4.2. Isolation of Human Peripheral Blood Mononuclear Cells
4.3. Aptamers
4.4. Antibody-Oligonucleotide Conjugation
4.5. Western Blotting Analysis of Cell Extracts
4.6. ELISA Assays
4.7. Confocal Microscopy
4.8. Cell Viability Assays
4.9. Determination of Tumor Cells Lysis
4.10. Effects of Immunomodulatory and Anti-TAA Drugs on Cytokine Release
4.11. Statistical Analyses
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
- Papaioannou, N.E.; Beniata, O.V.; Vitsos, P.; Tsitsilonis, O.; Samara, P. Harnessing the immune system to improve cancer therapy. Ann. Transl. Med. 2016, 4, 261. [Google Scholar] [CrossRef] [PubMed]
- Peggs, K.S.; Quezada, S.A.; Allison, J.P. Cancer immunotherapy: Co-stimulatory agonists and co-inhibitory antagonists. Clin. Exp. Immunol. 2009, 157, 9–19. [Google Scholar] [CrossRef] [PubMed]
- Lohrisch, C.; Piccart, M. ERBB2/neu as a predictive factor in breast cancer. Clin. Breast Cancer 2001, 2, 129–135. [Google Scholar] [CrossRef] [PubMed]
- Tagliabue, E.; Centis, F.; Campiglio, M.; Mastroianni, A.; Martignone, S.; Pellegrini, R.; Casalini, P.; Lanzi, C.; Ménard, S.; Colnaghi, M.I. Selection of monoclonal antibodies which induce internalization and phosphorylation of p185ERBB2 and growth inhibition of cells with ERBB2/NEU gene amplification. Int. J. Cancer 1991, 47, 933–937. [Google Scholar] [CrossRef] [PubMed]
- Slamon, D.J.; Godolphin, W.; Jones, L.A.; Holt, J.A.; Wong, S.G.; Keith, D.E.; Levin, W.J.; Stuart, S.G.; Udove, J.; Ullrich, A. Studies of the HER-2/neu proto-oncogene in human breast and ovarian cancer. Science 1989, 244, 707–712. [Google Scholar] [CrossRef] [PubMed]
- Sparano, J.A. Cardiac toxicity of trastuzumab (Herceptin): Implications for the design of adjuvant trials. Semin. Oncol. 2001, 28, 20–27. [Google Scholar] [CrossRef]
- Natha, R.; Yu, D.; Hung, M.C.; Hortobagyi, G.N.; Esteva, F.J. Mechanisms of disease: Understanding resistance to ERBB2-targeted therapy in human breast cancer. Nat. Clin. Pract. Oncol. 2006, 3, 269–280. [Google Scholar]
- Riccio, G.; Coppola, C.; Piscopo, G.; Capasso, I.; Maurea, C.; Esposito, E.; De Lorenzo, C.; Maurea, N. Trastuzumab and target-therapy side effects: Is still valid to differentiate anthracycline Type I from Type II cardiomyopathies? Hum. Vaccines Immunother. 2016, 12, 1124–1131. [Google Scholar] [CrossRef]
- Chung, C.; Lam, M.S. Pertuzumab for the treatment of human epidermal growth factor receptor type 2-positive metastatic breast cancer. Am. J. Health Syst. Pharm. 2013, 70, 1579–1587. [Google Scholar] [CrossRef]
- Baron, J.M.; Boster, B.L.; Barnett, C.M. Ado-trastuzumab emtansine (T-DM1): A novel antibody drug conjugate for the treatment of ERBB2-positive metastatic breast cancer. J Oncol. Pharm. Pract. 2015, 21, 132–142. [Google Scholar] [CrossRef]
- Maurea, N.; Coppola, C.; Piscopo, G.; Galletta, F.; Riccio, G.; Esposito, E.; De Lorenzo, C.; De Laurentiis, M.; Spallarossa, P.; Mercuro, G. Pathophysiology of cardiotoxicity from target therapy and angiogenesis inhibitors. J. Cardiovasc. Med. (Hagerstown) 2016, 17, S19–S26. [Google Scholar] [CrossRef] [PubMed]
- De Lorenzo, C.; Paciello, R.; Riccio, G.; Rea, D.; Barbieri, A.; Coppola, C.; Maurea, N. Cardiotoxic effects of the novel approved anti-ErbB2 agents and reverse cardioprotective effects of ranolazine. OncoTargets Ther. 2018, 11, 2241–2250. [Google Scholar] [CrossRef] [PubMed]
- De Lorenzo, C.; Palmer, D.B.; Piccoli, R.; Ritter, M.A.; D’Alessio, G. A new human antitumor immunoreagent specific for ErbB2. Clin. Cancer Res. 2002, 8, 1710–1719. [Google Scholar] [PubMed]
- De Lorenzo, C.; Arciello, A.; Cozzolino, R.; Palmer, D.B.; Laccetti, P.; Piccoli, R.; D’Alessio, G. A fully human antitumor immunoRNase selective for ErbB-2-positive carcinomas. Cancer Res. 2004, 64, 4870–4874. [Google Scholar] [CrossRef] [PubMed]
- De Lorenzo, C.; Tedesco, A.; Terrazzano, G.; Cozzolino, R.; Laccetti, P.; Piccoli, R.; D’Alessio, G. A human, compact, fully functional anti-ErbB2 antibody as a novel antitumour agent. Br. J. Cancer 2004, 91, 1200–1204. [Google Scholar] [CrossRef] [Green Version]
- Riccio, G.; Da Fonseca-Ricardo, A.R.; Passariello, M.; Cunnah, P.; Mertens, N.; De Lorenzo, C. Superior Suppression of ErbB2-positive Tumor Cells by a Novel Human Triparatopic Tribody. J. Immunother. 2017, 40, 117–128. [Google Scholar] [CrossRef] [PubMed]
- Riccio, G.; Ricardo, A.R.; Passariello, M.; Saraiva, K.; Rubino, V.; Cunnah, P.; Mertens, N.; De Lorenzo, C. T-cell Activating Tribodies as a Novel Approach for Efficient Killing of ErbB2-positive Cancer Cells. J. Immunother. 2019, 42, 1–10. [Google Scholar] [CrossRef]
- Troise, F.; Monti, M.; Merlino, A.; Cozzolino, F.; Fedele, C.; Russo Krauss, I.; Sica, F.; Pucci, P.; D’Alessio, G.; De Lorenzo, C. A novel ErbB2 epitope targeted by human antitumor immunoagents. FEBS J. 2011, 278, 1156–1166. [Google Scholar] [CrossRef]
- Fedele, C.; Riccio, G.; Coppola, C.; Barbieri, A.; Monti, M.G.; Arra, C.; Tocchetti, C.G.; D’Alessio, G.; Maurea, N.; De Lorenzo, C. Comparison of preclinical cardiotoxic effects of different ErbB2 inhibitors. Breast Cancer Res. Treat. 2012, 133, 511–521. [Google Scholar] [CrossRef]
- Riccio, G.; Esposito, G.; Leoncini, E.; Contu, R.; Condorelli, G.; Chiariello, M.; Laccetti, P.; Hrelia, S.; D’Alessio, G.; De Lorenzo, C. Cardiotoxic effects, or lack thereof, of anti-ErbB2 immunoagents. FASEB J. 2009, 23, 3171–3178. [Google Scholar] [CrossRef]
- Brahmer, J.R.; Tykodi, S.S.; Chow, L.Q.; Hwu, W.J.; Topalian, S.L.; Hwu, P.; Drake, C.G.; Camacho, L.H.; Kauh, J.; Odunsi, K.; et al. Safety and activity of anti-PD-L1 antibody in patients with advanced cancer. N. Engl. J. Med. 2012, 366, 2455–2465. [Google Scholar] [CrossRef] [PubMed]
- Patel, R.; Bock, M.; Polotti, C.F.; Elsamra, S. Pharmacokinetic drug evaluation of atezolizumab for the treatment of locally advanced or metastatic urothelial carcinoma. Expert Opin. Drug Metab. Toxicol. 2017, 13, 225–232. [Google Scholar] [CrossRef] [PubMed]
- Shultz, D. Three Drugs Approved for Urothelial Carcinoma by FDA. Cancer Discov. 2017, 7, 659–660. [Google Scholar]
- Callahan, M.K.; Flaherty, C.R.; Postow, M.A. Checkpoint Blockade for the Treatment of Advanced Melanoma. Cancer Treat. Res. 2016, 167, 231–250. [Google Scholar] [PubMed]
- Lee, C.S.; Cragg, M.; Glennie, M.; Johnson, P. Novel antibodies targeting immune regulatory checkpoints for cancer therapy. Br. J. Clin. Pharmacol. 2013, 76, 233–247. [Google Scholar] [CrossRef] [PubMed]
- Buqué, A.; Bloy, N.; Aranda, F.; Castoldi, F.; Eggermont, A.; Cremer, I.; Fridman, W.H.; Fucikova, J.; Galon, J.; Marabelle, A.; et al. Trial Watch: Immunomodulatory monoclonal antibodies for oncological indications. Oncoimmunology 2015, 4, e1008814. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Pardoll, D.M. The blockade of immune checkpoints in cancer immunotherapy. Nat. Rev. Cancer 2012, 12, 252–264. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Assal, A.; Kaner, J.; Pendurti, G.; Zang, X. Emerging targets in cancer immunotherapy: Beyond CTLA-4 and PD-1. Immunotherapy 2015, 7, 1169–1186. [Google Scholar] [CrossRef]
- Haile, S.T.; Dalal, S.P.; Clements, V.; Tamada, K.; Ostrand-Rosenberg, S. Soluble CD80 restores T cell activation and overcomes tumor cell programmed death ligand 1-mediated immune suppression. J. Immunol. 2013, 191, 2829–2836. [Google Scholar] [CrossRef]
- Reichert, J.M. Antibodies to watch in 2017. Mabs 2017, 9, 167–181. [Google Scholar] [CrossRef]
- Tan, H.Y.; Wang, N.; Lam, W.; Guo, W.; Feng, Y.; Cheng, Y.C. Targeting tumour microenvironment by tyrosine kinase inhibitor. Mol. Cancer 2018, 17, 43. [Google Scholar] [CrossRef] [PubMed]
- Wimberly, H.; Brown, J.R.; Schalper, K.; Haack, H.; Silver, M.R.; Nixon, C.; Bossuyt, V.; Pusztai, L.; Lannin, D.R.; Rimm, D.L. PD-L1 Expression Correlates with Tumor-Infiltrating Lymphocytes and Response to Neoadjuvant Chemotherapy in Breast Cancer. Cancer Immunol. Res. 2015, 3, 326–332. [Google Scholar] [CrossRef] [PubMed]
- Velcheti, V.; Schalper, K.A.; Carvajal, D.E.; Anagnostou, V.K.; Syrigos, K.N.; Sznol, M.; Herbst, R.S.; Gettinger, S.N.; Chen, L.; Rimm, D.L. Programmed death ligand-1 expression in non-small cell lung cancer. Lab. Investig. 2014, 94, 107–116. [Google Scholar] [CrossRef] [PubMed]
- Akbay, E.A.; Koyama, S.; Carretero, J.; Altabef, A.; Tchaicha, J.H.; Christensen, C.L.; Mikse, O.R.; Cherniack, A.D.; Beauchamp, E.M.; Pugh, T.J.; et al. Activation of the PD-1 pathway contributes to immune escape in EGFR-driven lung tumors. Cancer Discov. 2013, 3, 1355–1363. [Google Scholar] [CrossRef] [PubMed]
- Li, X.; Lian, Z.; Wang, S.; Xing, L.; Yu, J. Interactions between EGFR and PD-1/PD-L1 pathway: Implications for treatment of NSCLC. Cancer Lett. 2018, 418, 1–9. [Google Scholar] [CrossRef] [PubMed]
- Azuma, K.; Ota, K.; Kawahara, A.; Hattori, S.; Iwama, E.; Harada, T.; Matsumoto, K.; Takayama, K.; Takamori, S.; Kage, M.; et al. Association of PD-L1 overexpression with activating EGFR mutations in surgically resected nonsmall-cell lung cancer. Ann. Oncol. 2014, 25, 1935–1940. [Google Scholar] [CrossRef]
- Chen, N.; Fang, W.; Zhan, J.; Hong, S.; Tang, Y.; Kang, S.; Zhang, Y.; He, X.; Zhou, T.; Qin, T.; et al. Upregulation of PD-L1 by EGFR activation mediates the Immune Escape in EGFR-Driven NSCLC: Implication for Optional Immune Targeted Therapy for NSCLC Patients with EGFR Mutation. J. Thorac. Oncol. 2015, 10, 910–923. [Google Scholar] [CrossRef]
- D’incecco, A.; Andreozzi, M.; Ludovini, V.; Rossi, E.; Capodanno, A.; Landi, L.; Tibaldi, C.; Minuti, G.; Salvini, J.; Coppi, E.; et al. PD-1 and PD-L1 expression in molecularly selected non-small-cell lung cancer patients. Br. J. Cancer 2015, 112, 95–102. [Google Scholar] [CrossRef]
- ClinicalTrials.gov. Clinical Trial of Atezolizumab with Paclitaxel, Trastuzumab, and Pertuzumab in Patients with Metastatic HER-2 Positive Breast Cancer; ClinicalTrials.gov: Philadelphia, PA, USA, 2019; NCT03125928.
- De Melo Gagliato, D.; Cortes, J.; Curigliano, G.; Loi, S.; Denkert, C.; Perez-Garcia, J.; Holgado, E. Tumor-infiltrating lymphocytes in Breast Cancer and implications for clinical practice. Biochim. Biophys. Acta 2017, 1868, 527–537. [Google Scholar] [CrossRef]
- Gainor, J.F.; Shaw, A.T.; Sequist, L.V.; Fu, X.; Azzoli, C.G.; Piotrowska, Z.; Huynh, T.G.; Zhao, L.; Fulton, L.; Schultz, K.R.; et al. EGFR mutations and ALK rearrangements are associated with low response rates to PD-1 pathway blockade in non-small cell lung cancer: A retrospective analysis. Clin. Cancer Res. 2016, 22, 4585–4593. [Google Scholar] [CrossRef]
- Camorani, S.; Crescenzi, E.; Fedele, M.; Cerchia, L. Oligonucleotide aptamers against tyrosine kinase receptors: Prospect for anticancer applications. BBA Rev. Cancer 2018, 1869, 263–277. [Google Scholar] [CrossRef] [PubMed]
- Keefe, A.D.; Pai, S.; Ellington, A. Aptamers as therapeutics. Nat. Rev. Drug Discov. 2010, 9, 537–550. [Google Scholar] [CrossRef] [PubMed]
- Esposito, C.L.; Passaro, D.; Longobardo, I.; Condorelli, G.; Marotta, P.; Affuso, A.; de Franciscis, V.; Cerchia, L. A neutralizing RNA aptamer against EGFR causes selective apoptotic cell death. PLoS ONE 2011, 6, e24071. [Google Scholar] [CrossRef] [PubMed]
- Camorani, S.; Esposito, C.L.; Rienzo, A.; Catuogno, S.; Iaboni, M.; Condorelli, G.; De Franciscis, V.; Cerchia, L. Inhibition of Receptor Signaling and of Glioblastoma-derived Tumor Growth by a Novel PDGFRβ Aptamer. Mol. Ther. 2014, 22, 828–841. [Google Scholar] [CrossRef] [PubMed]
- Camorani, S.; Crescenzi, E.; Colecchia, D.; Carpentieri, A.; Amoresano, A.; Fedele, M.; Chiariello, M.; Cerchia, L. Aptamer targeting EGFRvIII mutant hampers its constitutive autophosphorylation and affects migration, invasion and proliferation of glioblastoma cells. Oncotarget 2015, 6, 37570–37587. [Google Scholar] [CrossRef] [PubMed]
- Camorani, S.; Crescenzi, E.; Gramanzini, M.; Fedele, M.; Zannetti, A.; Cerchia, L. Aptamer-mediated impairment of EGFR-integrin avβ3 complex inhibits vasculogenic mimicry and growth of triple-negative breast cancers. Sci. Rep. 2017, 7, 46659. [Google Scholar] [CrossRef] [PubMed]
- Shu, D.; Li, H.; Shu, Y.; Xiong, G.; Carson, W.E., III; Haque, F.; Xu, R.; Guo, P. Systemic Delivery of Anti-miRNA for Suppression of Triple Negative Breast Cancer Utilizing RNA Nanotechnology. ACS Nano 2015, 9, 9731–9740. [Google Scholar] [CrossRef] [PubMed]
- Zheng, L.; Tan, W.; Zhang, J.; Yuan, D.; Yang, J.; Liu, H. Combining trastuzumab and cetuximab combats trastuzumab-resistant gastric cancer by effective inhibition of EGFR/ErbB2 heterodimerization and signaling. Cancer Immunol. Immunother. 2014, 63, 581–586. [Google Scholar] [CrossRef]
- Zhou, Y.; Li, S.; Hu, Y.P.; Wang, J.; Hauser, J.; Conway, A.N.; Vinci, M.A.; Humphrey, L.; Zborowska, E.; Willson, J.K.; et al. Blockade of EGFR and ErbB2 by the novel dual EGFR and ErbB2 tyrosine kinase inhibitor GW572016 sensitizes human colon carcinoma GEO cells to apoptosis. Cancer Res. 2006, 66, 404–411. [Google Scholar] [CrossRef]
- Xia, W.; Lau, Y.K.; Zhang, H.Z.; Xiao, F.Y.; Johnston, D.A.; Liu, A.R.; Li, L.; Katz, R.L.; Hung, M.C. Combination of EGFR, HER-2/neu, and HER-3 is a stronger predictor for the outcome of oral squamous cell carcinoma than any individual family members. Clin. Cancer Res. 1999, 5, 4164–4174. [Google Scholar]
- Pignon, J.C.; Koopmansch, B.; Nolens, G.; Delacroix, L.; Waltregny, D.; Winkler, R. Androgen receptor controls EGFR and ERBB2 gene expression at different levels in prostate cancer cell lines. Cancer Res. 2009, 69, 2941–2949. [Google Scholar] [CrossRef] [PubMed]
- Kawai, S.; Kato, S.; Imai, H.; Okada, Y.; Ishioka, C. Suppression of FUT1 attenuates cell proliferation in the HER2-overexpressing cancer cell line NCI-N87. Oncol. Rep. 2013, 29, 13–20. [Google Scholar] [CrossRef] [PubMed]
- Wu, Y.; Li, R.; Zhang, J.; Wang, G.; Liu, B.; Huang, X.; Zhang, T.; Luo, R. Protein tyrosine phosphatase SHP-1 sensitizes EGFR/HER-2 positive breast cancer cells to trastuzumab through modulating phosphorylation of EGFR and HER-2. Onco Targets Ther. 2015, 8, 2577–2587. [Google Scholar] [PubMed] [Green Version]
- Cembrola, B.; Ruzza, V.; Troise, F.; Esposito, M.L.; Sasso, E.; Cafaro, V.; Passariello, M.; Visconte, F.; Raia, M.; Del Vecchio, L.; et al. Rapid affinity maturation of novel anti-PD-L1 antibodies by a fast drop of the antigen concentration and FACS selection of yeast libraries. BioMed Res. Int. J 2019. (under minor revision). [Google Scholar]
- Suh, K.J.; Sung, J.H.; Kim, J.W.; Han, S.H.; Lee, H.S.; Min, A.; Kang, M.H.; Kim, J.E.; Kim, J.W.; Kim, S.H.; et al. EGFR or HER2 inhibition modulates the tumor microenvironment by suppression of PD-L1 and cytokines release. Oncotarget 2017, 8, 63901–63910. [Google Scholar] [CrossRef] [PubMed]
- Wang, X.; Yang, L.; Huang, F.; Zhang, Q.; Liu, S.; Ma, L.; You, Z. Inflammatory cytokines IL-17 and TNF-α up-regulate PD-L1 expression in human prostate and colon cancer cells. Immunol. Lett. 2017, 184, 7–14. [Google Scholar] [CrossRef] [PubMed]
- Passariello, M.; D’Alise, M.A.; Esposito, A.; Vetrei, C.; Froechlich, G.; Scarselli, E.; Nicosia, A.; De Lorenzo, C. Novel human anti-PD-L1 mAbs inhibit immune-independent tumor cell growth and PD-L1 associated intracellular signalling. Sci. Rep. 2019. (accepted). [Google Scholar]
- Gatalica, Z.; Snyder, C.; Maney, T.; Ghazalpour, A.; Holterman, D.A.; Xiao, N.; Overberg, P.; Rose, I.; Basu, G.D.; Vranic, S.; et al. Programmed cell death 1 (PD-1) and its ligand (PD-L1) in common cancers and their correlation with molecular cancer type. Cancer Epidemiol. Prev. Biomark. 2014, 23, 2965–2970. [Google Scholar] [CrossRef]
- Sasso, E.; D’Avino, C.; Passariello, M.; D’Alise, A.M.; Siciliano, D.; Esposito, M.L.; Froechlich, G.; Cortese, R.; Scarselli, E.; Zambrano, N.; et al. Massive parallel screening of phage libraries for the generation of repertoires of human immunomodulatory monoclonal antibodies. MAbs 2018, 10, 1060–1072. [Google Scholar] [CrossRef]
- Decker, T.; Lohmann-Matthes, M.L. A quick and simple method for the quantitation of lactate dehydrogenase release in measurements of cellular cytotoxicity and tumor necrosis factor (TNF) activity. J. Immunol. Methods 1988, 115, 61–69. [Google Scholar] [CrossRef]
- Kozlov, I.A.; Melnyk, P.C.; Stromsborg, K.E.; Chee, M.S.; Barker, D.L.; Zhao, C. Efficient strategies for the conjugation of oligonucleotides to antibodies enabling highly sensitive protein detection. Biopolymers 2004, 73, 621–630. [Google Scholar] [CrossRef] [PubMed]
- Rom-Jurek, E.M.; Kirchhammer, N.; Ugocsai, P.; Ortmann, O.; Wege, A.; Brockhoff, G. Regulation of Programmed Death Ligand 1 (PD-L1) Expression in Breast Cancer Cell Lines in Vitro and in Immunodeficient and Humanized Tumor Mice. Int. J. Mol. Sci. 2018, 19, 563. [Google Scholar] [CrossRef] [PubMed]
- Hori, S.I.; Herrera, A.; Rossi, J.J.; Zhou, J. Current Advances in Aptamers for Cancer Diagnosis and Therapy Cancers. Cancers 2018, 10, 9. [Google Scholar] [CrossRef] [PubMed]
- Chiavenna, S.M.; Jaworski, J.P.; Vendrell, A. State of the art in anti-cancer mAbs. J. Biomed. Sci. 2017, 24, 15. [Google Scholar] [CrossRef] [PubMed]
- Chames, P.; Van Regenmortel, M.; Weiss, E.; Baty, D. Therapeutic antibodies: Successes, limitations and hopes for the future. Br. J. Pharmacol. 2009, 157, 220–233. [Google Scholar] [CrossRef] [PubMed]
- Beckman, R.A.; Weiner, L.M.; Davis, H.M. Antibody constructs in cancer therapy: Protein engineering strategies to improve exposure in solid tumors. Cancer 2007, 109, 170–179. [Google Scholar] [CrossRef] [PubMed]
- Heo, K.; Min, S.W.; Sung, H.J.; Kim, H.G.; Kim, H.J.; Kim, Y.H.; Choi, B.K.; Han, S.; Chung, S.; Lee, E.S.; et al. An aptamer-antibody complex (oligobody) as a novel delivery platform for targeted cancer therapies. J. Control. Release 2016, 229, 1–9. [Google Scholar] [CrossRef]
- Dickgiesser, S.; Rasche, N.; Nasu, D.; Middel, S.; Hörner, S.; Avrutina, O.; Diederichsen, U.; Kolmar, H. Self-Assembled Hybrid Aptamer-Fc Conjugates for Targeted Delivery: A Modular Chemoenzymatic Approach. ACS Chem. Biol. 2015, 10, 2158–2165. [Google Scholar] [CrossRef]
- De Lorenzo, C.; D’Alessio, G. Human anti-ErbB2 immunoagents--immunoRNases and compact antibodies. FEBS J. 2009, 276, 1527–1535. [Google Scholar] [CrossRef]
- De Lorenzo, C.; Cozzolino, R.; Carpentieri, A.; Pucci, P.; Laccetti, P.; D’Alessio, G. Biological properties of a human compact anti-ErbB2 antibody. Carcinogenesis 2005, 26, 1890–1895. [Google Scholar] [CrossRef] [Green Version]
- Gelardi, T.; Damiano, V.; Rosa, R.; Bianco, R.; Cozzolino, R.; Tortora, G.; Laccetti, P.; D’alessio, G.; De Lorenzo, C. Two novel human anti-ErbB2 immunoagents are active on trastuzumab-resistant tumours. Br. J. Cancer 2010, 102, 513–519. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Fedele, C.; Carvalho, S.; Riccio, G.; Paciello, R.; Laccetti, P.; Schmitt, F.; De Lorenzo, C. Effects of a human compact anti-ErbB2 antibody on gastric cancer. Gastric Cancer 2014, 17, 107–115. [Google Scholar] [CrossRef] [PubMed]
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Passariello, M.; Camorani, S.; Vetrei, C.; Cerchia, L.; De Lorenzo, C. Novel Human Bispecific Aptamer–Antibody Conjugates for Efficient Cancer Cell Killing. Cancers 2019, 11, 1268. https://doi.org/10.3390/cancers11091268
Passariello M, Camorani S, Vetrei C, Cerchia L, De Lorenzo C. Novel Human Bispecific Aptamer–Antibody Conjugates for Efficient Cancer Cell Killing. Cancers. 2019; 11(9):1268. https://doi.org/10.3390/cancers11091268
Chicago/Turabian StylePassariello, Margherita, Simona Camorani, Cinzia Vetrei, Laura Cerchia, and Claudia De Lorenzo. 2019. "Novel Human Bispecific Aptamer–Antibody Conjugates for Efficient Cancer Cell Killing" Cancers 11, no. 9: 1268. https://doi.org/10.3390/cancers11091268