Research Topics
| ROBERT SHARKEYSummaryAffiliation: Garden State Cancer Center Country: USA Publications
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Publications
Pretargeting: taking an alternate route for localizing radionuclidesRobert M Sharkey
Garden State Cancer Center at the Center for Molecular Medicine and Immunology, 300 The American Road, Morris Plains, 07950, NJ, USA
Tumour Biol 33:591-600. 2012..In this article, we review the progress our group has made toward developing and testing bsMAb pretargeting systems for cancer detection and therapy...
Pretargeted versus directly targeted radioimmunotherapy combined with anti-CD20 antibody consolidation therapy of non-Hodgkin lymphomaRobert M Sharkey
Garden State Cancer Center at the Center for Molecular Medicine and Immunology, Belleville, New Jersey 07109, USA
J Nucl Med 50:444-53. 2009....
A re-examination of radioimmunotherapy in the treatment of non-Hodgkin lymphoma: prospects for dual-targeted antibody/radioantibody therapyRobert M Sharkey
Garden State Cancer Center, Center for Molecular Medicine and Immunology, Belleville, NJ 07109, USA
Blood 113:3891-5. 2009..This perspective discusses how these issues could affect current and future clinical trials...
Novel radioimmunopharmaceuticals for cancer imaging and therapyRobert M Sharkey
Garden State Cancer Center, at the Center for Molecular Medicine and Immunology, 520 Belleville Ave, Belleville, NJ 07109, USA
Curr Opin Investig Drugs 9:1302-16. 2008..Whether directly coupled to a radionuclide or used in a pretargeting setting, radioimmunoconjugates are being reinvented to meet the many challenges facing cancer detection and therapy today and in the future...
The direct route may not be the best way to homeRobert M Sharkey
Center for Molecular Medicine and Immunology Belleville, NJ 07109, USA
J Nucl Med 46:391-4. 2005
Radioimmunotherapy against the tumor vasculature: A new target?Robert M Sharkey
Center for Molecular Medicine and Immunology, Belleville, New Jersey 07109, USA
J Nucl Med 47:1070-4. 2006
Improved therapeutic results by pretargeted radioimmunotherapy of non-Hodgkin's lymphoma with a new recombinant, trivalent, anti-CD20, bispecific antibodyRobert M Sharkey
Garden State Cancer Center, Center for Molecular Medicine and Immunology, Belleville, New Jersey 07109, USA
Cancer Res 68:5282-90. 2008..These encouraging results prompt testing these constructs for pretargeting RAIT in patients...
Use of antibodies and immunoconjugates for the therapy of more accessible cancersRobert M Sharkey
Garden State Cancer Center, Center for Molecular Medicine and Immunology, Belleville, NJ 07109, USA
Adv Drug Deliv Rev 60:1407-20. 2008....
Metastatic human colonic carcinoma: molecular imaging with pretargeted SPECT and PET in a mouse modelRobert M Sharkey
Center for Molecular Medicine and Immunology, Garden State Cancer Center, 520 Belleville Ave, Belleville, NJ 07109, USA
Radiology 246:497-507. 2008..To prospectively determine if a bispecific monoclonal antibody (MoAb) pretargeting method with a radiolabeled hapten peptide can depict small (<0.3 mm in diameter) microdisseminated human colon cancer colonies in the lungs of nude mice...
Bispecific antibody pretargeting of radionuclides for immuno single-photon emission computed tomography and immuno positron emission tomography molecular imaging: an updateRobert M Sharkey
Garden State Cancer Center, Center for Molecular Medicine and Immunology, Belleville, New Jersey, USA
Clin Cancer Res 13:5577s-5585s. 2007..Thus, this bispecific antibody pretargeting procedure may contribute to tumor detection and could also contribute to the detection of other diseases having distinct antigen targets and suitably specific antibodies...
Radioimmunotherapy of non-Hodgkin's lymphoma with 90Y-DOTA humanized anti-CD22 IgG (90Y-Epratuzumab): do tumor targeting and dosimetry predict therapeutic response?Robert M Sharkey
Garden State Cancer Center, Center for Molecular Medicine and Immunology, Belleville, New Jersey 07109, USA
J Nucl Med 44:2000-18. 2003..Of particular interest was to evaluate whether pretherapy targeting and tumor dosimetry could predict therapeutic responses...
Combination radioimmunotherapy and chemoimmunotherapy involving different or the same targets improves therapy of human pancreatic carcinoma xenograft modelsRobert M Sharkey
Garden State Cancer Center, Center for Molecular Medicine and Immunology, 300 American Way, Morris Plains, NJ 07950, USA
Mol Cancer Ther 10:1072-81. 2011..These studies show the feasibility of combining ADC and RAIT for improved efficacy without increased toxicity...
Epratuzumab-SN-38: a new antibody-drug conjugate for the therapy of hematologic malignanciesRobert M Sharkey
Garden State Cancer Center, 300 American Road, Morris Plains, New Jersey 07950, USA
Mol Cancer Ther 11:224-34. 2012..Thus, Emab-SN-38 is active in lymphoma and leukemia at doses well below toxic levels and therefore represents a new promising agent with therapeutic potential alone or combined with anti-CD20 antibody therapy...
Improving the treatment of non-Hodgkin lymphoma with antibody-targeted radionuclidesRobert M Sharkey
Center for Molecular Medicine and Immunology, Garden State Cancer Center, 520 Belleville Avenue, Belleville, NJ 07109, USA
Cancer 116:1134-45. 2010..This article reviews these various options and discusses how some fundamental changes could potentially enhance the response and duration from radionuclide-targeted therapy...
Cancer radioimmunotherapyRobert M Sharkey
Garden State Cancer Center, Belleville, NJ 07109, USA
Immunotherapy 3:349-70. 2011..Novel antibody constructs, focusing on treatment of localized and minimal disease, and pretargeting are all promising new approaches that are currently under investigation...
Optimizing bispecific antibody pretargeting for use in radioimmunotherapyRobert M Sharkey
Center for Molecular Medicine and Immunology, Belleville, New Jersey 07109, USA
Clin Cancer Res 9:3897S-913S. 2003....
Recombinant bispecific monoclonal antibodies prepared by the dock-and-lock strategy for pretargeted radioimmunotherapyRobert M Sharkey
Garden State Cancer Center, Center for Molecular Medicine and Immunology, Belleville, NJ, USA
Semin Nucl Med 40:190-203. 2010....
Bispecific antibody pretargeting PET (immunoPET) with an 124I-labeled hapten-peptideWilliam J McBride
Immunomedics, Inc, Morris Plains, New Jersey, USA
J Nucl Med 47:1678-88. 2006....
Improved targeting of pancreatic cancer: experimental studies of a new bispecific antibody, pretargeting enhancement system for immunoscintigraphyThomas M Cardillo
Garden State Cancer Center, Belleville, New Jersey 07109, USA
Clin Cancer Res 10:3552-61. 2004..The advantage of pretargeted bsPAM4 antibody as an imaging platform is the high specificity for pancreatic cancer as compared with the physicochemical parameters identified by current imaging technologies...
Signal amplification in molecular imaging by pretargeting a multivalent, bispecific antibodyRobert M Sharkey
Garden State Cancer Center, Center for Molecular Medicine and Immunology, 520 Belleville Avenue, Belleville, New Jersey 07109, USA
Nat Med 11:1250-5. 2005..This technology could be adapted to other antibodies and imaging modalities...
Therapy of advanced B-lymphoma xenografts with a combination of 90Y-anti-CD22 IgG (epratuzumab) and unlabeled anti-CD20 IgG (veltuzumab)M Jules Mattes
Garden State Cancer Center, Center for Molecular Medicine and Immunology, 520 Belleville Avenue, Belleville, NJ 07109, USA
Clin Cancer Res 14:6154-60. 2008..In this study, the combination of a new unconjugated humanized anti-CD20 IgG, veltuzumab, with a (90)Y-conjugated humanized antibody to CD22 (epratuzumab) was evaluated for the treatment of B-cell lymphoma in a nude mouse model system...
Therapeutic advantage of pretargeted radioimmunotherapy using a recombinant bispecific antibody in a human colon cancer xenograftHabibe Karacay
Center for Molecular Medicine and Immunology and the Garden State Cancer Center, Belleville, NJ 07109, USA
Clin Cancer Res 11:7879-85. 2005..CONCLUSION: Pretargeting increases the amount of radioactivity delivered to colorectal tumors sufficiently to improve the therapeutic index and responses as compared with conventional radioimmunotherapy...
Reagents and methods for PET using bispecific antibody pretargeting and 68Ga-radiolabeled bivalent hapten-peptide-chelate conjugatesGary L Griffiths
Immunomedics, Inc, Morris Plains, New Jersey Garden State Cancer Center, Belleville, New Jersey 07950, USA
J Nucl Med 45:30-9. 2004..The aim of this work was to develop reagents and methods potentially useful in PET, using (68)Ga in a 2-step pretargeting protocol...
A universal pretargeting system for cancer detection and therapy using bispecific antibodyRobert M Sharkey
Center for Molecular Medicine and Immunology, Belleville, New Jersey 07109, USA
Cancer Res 63:354-63. 2003..These results suggest that this multistep, pretargeting system has diagnostic imaging and therapeutic potential...
Multifunctional antibodies by the Dock-and-Lock method for improved cancer imaging and therapy by pretargetingDavid M Goldenberg
Garden State Cancer Center, Center for Molecular Medicine and Immunology, Belleville, New Jersey 07109, USA
J Nucl Med 49:158-63. 2008..Improved therapeutic efficacy is shown with pretargeting in a pancreatic cancer xenograft model given a tri-Fab to a pancreatic cancer MUC1 and the hapten peptide labeled with (90)Y...
Radioimmunotherapy: is avidin-biotin pretargeting the preferred choice among pretargeting methods?David M Goldenberg
Center for Molecular Medicine and Immunology, Garden State Cancer Center, 520 Belleville Avenue, NJ 07109-0023, Belleville, USA
Eur J Nucl Med Mol Imaging 30:777-80. 2003
Perspectives on cancer therapy with radiolabeled monoclonal antibodiesRobert M Sharkey
Garden State Cancer Center, Center for Molecular Medicine and Immunology, Belleville, NJ 07109, USA
J Nucl Med 46:115S-27S. 2005..There is also optimism that pretargeting procedures, including new molecular constructs and targets, will improve the delivery of radioactivity to tumors, do so with less hematologic toxicity, and become the next generation of RIT...
Pretargeted radioimmunotherapy of pancreatic cancer xenografts: TF10-90Y-IMP-288 alone and combined with gemcitabineHabibe Karacay
Center for Molecular Medicine and Immunology, Belleville, New Jersey 07109, USA
J Nucl Med 50:2008-16. 2009..The studies reported herein examine a new pretargeting procedure for delivering therapeutic radionuclides...
Targeted therapy of cancer: new prospects for antibodies and immunoconjugatesRobert M Sharkey
Center for Molecular Medicine and Immunology, Belleville, NJ, USA
CA Cancer J Clin 56:226-43. 2006..We review how antibodies and immunoconjugates have influenced cancer detection and therapy, and also describe promising new developments and challenges for broader applications...
Advances in radioimmunotherapy in the age of molecular engineering and pretargetingRobert M Sharkey
Garden State Cancer Center at the Center for Molecular Medicine and Immunology, Belleville, NJ 07109, USA
Cancer Invest 24:82-97. 2006..This review will discuss some of these promising new developments...
A novel bispecific, trivalent antibody construct for targeting pancreatic carcinomaDavid V Gold
Garden State Cancer Center, Center for Molecular Medicine and Immunology, Belleville, New Jersey, USA
Cancer Res 68:4819-26. 2008..Thus, the results suggest that TF10 pretargeting may provide improved imaging for early detection, diagnosis, and treatment of pancreatic cancer as compared with directly radiolabeled PAM4-IgG...
New MUC1 serum immunoassay differentiates pancreatic cancer from pancreatitisDavid V Gold
Garden State Cancer Center at the Center for Molecular Medicine and Immunology, Belleville, NJ 07109, USA
J Clin Oncol 24:252-8. 2006..The sensitivity and specificity of the assay are examined and compared to results from a CA19-9 immunoassay...
Antibody pretargeting advances cancer radioimmunodetection and radioimmunotherapyDavid M Goldenberg
Garden State Cancer Center, Center for Molecular Medicine and Immunology, Belleville, NJ 07109, USA
J Clin Oncol 24:823-34. 2006....
Induction of apoptosis by cross-linking antibodies bound to human B-lymphoma cells: expression of Annexin V binding sites on the antibody capM Jules Mattes
Garden State Cancer Center at the Center for Molecular Medicine and Immunology, Belleville, NJ 07109, USA
Cancer Biother Radiopharm 24:185-93. 2009..Further studies are required to explain why Annexin V binding sites are exposed in the region of an Ab cap...
A divalent hapten-peptide induces apoptosis in human non hodgkin lymphoma cell lines targeted by anti-CD20xanti-hapten bispecific antibodiesPierre Yves Brard
Center for Molecular Medicine and Immunology, Belleville, New Jersey, 07109, USA
Clin Cancer Res 13:5564s-5571s. 2007..The goal of this study was to determine if a divalent hapten-peptide could induce apoptosis by cross-linking bsMAb bound to CD20...
Improving the delivery of radionuclides for imaging and therapy of cancer using pretargeting methodsRobert M Sharkey
Center for Molecular Medicine and Immunology, Belleville, New Jersey 10709, USA
Clin Cancer Res 11:7109s-7121s. 2005..Thus, the next generation of targeting agents will likely employ pretargeting approaches to optimize radionuclide delivery for a wide range of applications...
A phase I trial combining high-dose 90Y-labeled humanized anti-CEA monoclonal antibody with doxorubicin and peripheral blood stem cell rescue in advanced medullary thyroid cancerRobert M Sharkey
Center for Molecular Medicine and Immunology, Garden State Cancer Center, Belleville, New Jersey 07109, USA
J Nucl Med 46:620-33. 2005..Evidence of antitumor response in these patients with advanced cancer was modest, but encouraging; this type of treatment may be more successful if applied to more limited, earlier-stage disease...
Phase I radioimmunotherapy trial with iodine-131--labeled humanized MN-14 anti-carcinoembryonic antigen monoclonal antibody in patients with metastatic gastrointestinal and colorectal cancerGeorge Hajjar
Garden State Cancer Center, 520 Belleville Ave, Belleville, NJ 07109, USA
Clin Colorectal Cancer 2:31-42. 2002..In conclusion, 131I-hMN-14 IgG has good targeting, good tumor to normal organs radiation absorbed ratios, and an acceptable toxicity profile in advanced metastatic gastrointestinal and colorectal cancer patients...
Improved cancer therapy and molecular imaging with multivalent, multispecific antibodiesRobert M Sharkey
Center for Molecular Medicine and Immunology CMMI, Belleville, New Jersey, USA
Cancer Biother Radiopharm 25:1-12. 2010..Thus, DNL technology is a highly flexible platform that can be used to prepare many different types of agents that could further improve cancer detection and therapy...
Meeting report on the Ninth Conference on Cancer Therapy with Antibodies and ImmunoconjugatesRobert M Sharkey
Center for Molecular Medicine and Immunology, Garden State Cancer Center, 520 Belleville Avenue, Belleville, NJ 07945, USA
Cancer Res 63:8069-71. 2003....
Development of new multivalent-bispecific agents for pretargeting tumor localization and therapyEdmund A Rossi
IBC Pharmaceuticals, Inc, Morris Plains, New Jersey 07950, USA
Clin Cancer Res 9:3886S-96S. 2003..BS6 and BS8 may be even more attractive because of their potential to achieve higher levels of tumor uptake because of divalent carcinoembryonic antigen binding...
90Y-DOTA-hLL2: an agent for radioimmunotherapy of non-Hodgkin's lymphomaGary L Griffiths
Immunomedics, Incorporated, Morris Plains, New Jersey 07950, USA
J Nucl Med 44:77-84. 2003....
Red marrow radiation dose adjustment using plasma FLT3-L cytokine levels: improved correlations between hematologic toxicity and bone marrow dose for radioimmunotherapy patientsJeffry A Siegel
Nuclear Physics Enterprises, Cherry Hill, New Jersey 08003, USA
J Nucl Med 44:67-76. 2003....
Stably tethered multifunctional structures of defined composition made by the dock and lock method for use in cancer targetingEdmund A Rossi
IBC Pharmaceuticals, Inc, 300 American Road, Morris Plains, NJ 07950, USA
Proc Natl Acad Sci U S A 103:6841-6. 2006....
Use of ibritumomab tiuxetan anti-CD20 radioimmunotherapy in a non-Hodgkin's lymphoma patient previously treated with a yttrium-90-labeled anti-CD22 monoclonal antibodyDonald E Tsai
Bone Marrow and Stem Cell Transplant Program, University of Pennsylvania Cancer Center, Philadelphia, 19104, USA
Clin Lymphoma 4:56-9. 2003..This case report demonstrates the potential for repeated treatments with radioimmunotherapy agents in patients with chemotherapy-refractory non-Hodgkin's lymphoma...
Clinical-scale radiolabeling of a humanized anticarcinoembryonic antigen monoclonal antibody, hMN-14, with residualizing 131I for use in radioimmunotherapySerengulam V Govindan
Immunomedics, Inc, 300 American Rd, Morris Plains, NJ 07950, USA
J Nucl Med 46:153-9. 2005..IMP-R4 is MCC-Lys(MCC)-Lys(X)-d-Tyr-d-Lys(X)-OH, where MCC is 4-(N-maleimidomethyl)-cyclohexane-1-carbonyl and X is 1-((4-thiocarbonylamino)benzyl)-diethylenetriaminepentaacetic acid...
Radioimmunotherapy of non-Hodgkin's lymphoma revisitedDavid M Goldenberg
J Nucl Med 46:383-4. 2005
Blood-based red marrow dosimetry: where's the beef?Jeffry A Siegel
J Nucl Med 46:1404-6; author reply 1405-6. 2005
Pretargeting of carcinoembryonic antigen-expressing cancers with a trivalent bispecific fusion protein produced in myeloma cellsEdmund A Rossi
IBC Pharmaceuticals, Inc, Morris Plains, Jew Jersey, USA
Clin Cancer Res 11:7122s-7129s. 2005..CONCLUSIONS: The results indicate that hBS14 is an attractive candidate for use in a variety of pretargeting applications, particularly tumor therapy with radionuclides and drugs...
Bispecific antibody pretargeting of tumor neovasculature for improved systemic radiotherapy of solid tumorsDieter Moosmayer
Schering AG, Research Laboratories, Berlin, Germany
Clin Cancer Res 12:5587-95. 2006....
Survival improvement in patients with medullary thyroid carcinoma who undergo pretargeted anti-carcinoembryonic-antigen radioimmunotherapy: a collaborative study with the French Endocrine Tumor GroupJean Francois Chatal
Department of Nuclear Medicine, Institut Régional du Cancer, Nantes, France
J Clin Oncol 24:1705-11. 2006..The efficacy of pretargeted radioimmunotherapy (pRAIT) with bispecific monoclonal antibody (BsMAb) and a iodine-131 (131I) -labeled bivalent hapten is evaluated...
Molecular advances in pretargeting radioimunotherapy with bispecific antibodiesChien-Hsing Chang
IBC Pharmaceuticals, L. L. C, Morris Plains, New Jersey 07950, USA
Mol Cancer Ther 1:553-63. 2002..In addition, both preclinical and clinical results obtained from a pretargeting method known as the Affinity Enhancement System are presented. Future directions of pretargeting technology are also suggested...
Research Grants
- Bispecific Antibody Pretargeted Therapy of Pancreatic CancerROBERT SHARKEY; Fiscal Year: 2007..e., cetuximab and erlotinib) can further enhance this combination. Overall, these studies will assist in establishing whether this type of pretargeting approach could have a role in the clinical management of pancreatic cancer. ..
- Bispecific Antibody Pretargeting for TherapyROBERT SHARKEY; Fiscal Year: 2007..Anti-antibody responses will also be measured to the humanized bsMAb. This clinical trial will be conducted at the Fox Chase Cancer Center. ..
- RAIT of Pancreatic Cancer with Humanized PAM4ROBERT SHARKEY; Fiscal Year: 2005..The trial will be conducted at the Garden State Cancer Center and Johns Hopkins University School of Medicine. CMMI will be responsible for monitoring the study's progress. ..
- Improved Detection of Cancer Using Bi Specific AntibodyROBERT SHARKEY; Fiscal Year: 2003....
- Bispecific Antibody Pretargeting for TherapyROBERT SHARKEY; Fiscal Year: 2009..Anti-antibody responses will also be measured to the humanized bsMAb. This clinical trial will be conducted at the Fox Chase Cancer Center. ..
