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Lon J. Wilson - One of the best experts on this subject based on the ideXlab platform.
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Cell Internalization Studies of Gadofullerene-(ZME-018) Immunoconjugates into
2020Co-Authors: Christopher Scott Berger, Robert D. Bolskar, John W. Marks, M.g. Rosenblum, Lon J. WilsonAbstract:Fullerene (C60)–monoclonal antibody (mAb) Immunoconjugates have been determined to internalize into target cells using water-soluble Gd 3+ ion–filled metallofullerenes (Gd@C60[OH]x). Two separate conjugations of Gd@C60(OH)x with the antibody ZME-018 and a murine antibody mixture (MuIgG) were performed in a 1:5 mAb/Gd@C60 ratio. Characterization of the Immunoconjugates was established using inductively coupled plasma mass spectrometry (ICP-MS) for Gd 3+ and UV-Vis spectrometry (for Gd@C60 +C 60). Once conjugated, enzyme-linked immunosorbent assays showed little change in the specific binding of ZME-018. Each Immunoconjugate was exposed to two cancer cell lines, A375m (antigen positive), and T24, bladder carcinoma (antigen negative). Internalization levels of the Immunoconjugate were determined at various time points during 24 hours by harvesting and digesting the cells with 70% HNO3 for Gd 3+ ion analysis by ICP-MS. These results are the first to demonstrate the practicality of a targeted cancer therapy based on fullerene immunotherapy.
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Fullerene Immunoconjugates for Cancer Imaging and Treatment
2020Co-Authors: C Scott Berger, Robert D. Bolskar, Lon J. Wilson, M.g. Rosenblum, J. William MarksAbstract:Metallofullerene-paclitaxel-antibody conjugates are under investigation for combined cancer imaging and treatment. Fullerenes are non-toxic carbon cage molecules with a rich derivatization chemistry that is useful for generating covalently-conjugated therapeutic prodrugs [1]. Fullerene derivatives have been shown to spontaneously form non-covalent Immunoconjugates with antibodies such as the anti-gp240 melanoma antibody ZME-018; a recent study revealed how ZME-018 forms non-covalent Immunoconjugates with C60 derivatives without significant loss of antibody activity [2]. Endohedral gadofullerene derivatives have been shown in prior studies to function effectively as T1-active magnetic resonance imaging (MRI) contrast agents, both for in vivo MRI [3] and for in vitro cellular labeling [4].
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Cell Internalization Studies of Gadofullerene-(ZME-018) Immunoconjugates into A375m Melanoma Cells
Translational Oncology, 2011Co-Authors: Christopher Scott Berger, Robert D. Bolskar, John W. Marks, M.g. Rosenblum, Lon J. WilsonAbstract:Abstract Fullerene (C60)-monoclonal antibody (mAb) Immunoconjugates have been determined to internalize into target cells using water-soluble Gd3+ ion-filled metallofullerenes (Gd@C60[OH]x). Two separate conjugations of Gd@C60(OH)x with the antibody ZME-018 and a murine antibody mixture (MuIgG) were performed in a 1:5 mAb/Gd@C60 ratio. Characterization of the Immunoconjugates was established using inductively coupled plasma mass spectrometry (ICP-MS) for Gd3+ and UV-Vis spectrometry (for Gd@C60 + C60). Once conjugated, enzyme-linked immunosorbent assays showed little change in the specific binding of ZME-018. Each Immunoconjugate was exposed to two cancer cell lines, {A375m} (antigen positive), and T24, bladder carcinoma (antigen negative). Internalization levels of the Immunoconjugate were determined at various time points during 24 hours by harvesting and digesting the cells with 70% {HNO3} for Gd3+ ion analysis by ICP-MS. These results are the first to demonstrate the practicality of a targeted cancer therapy based on fullerene immunotherapy.
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Fullerene (C60) Immunoconjugates: interaction of water-soluble C60 derivatives with the murine anti-gp240 melanoma antibody
Chemical Communications, 2006Co-Authors: Jared M. Ashcroft, Dmitri A. Tsyboulski, Tatiana Y. Zakharian, John W. Marks, R. Bruce Weisman, Keith B. Hartman, M.g. Rosenblum, Lon J. WilsonAbstract:The first fullerene (C60) Immunoconjugates have been prepared and characterized as an initial step toward the development of fullerene immunotherapy (FIT).
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Fullerene Immunoconjugates for Cancer Imaging and Treatment
J. Am. Chem. Soc, 2005Co-Authors: C Scott Berger, Jay Collier, Robert D. Bolskar, Lon J. Wilson, M.g. Rosenblum, J William Marks IiiAbstract:The 217 th Meeting of the Electrochemical Society Vancouver, BC Canada – April 25-30, 2010 Metallofullerene-paclitaxel-antibody conjugates are under investigation for combined cancer imaging and treatment. Fullerenes are non-toxic carbon cage molecules with a rich derivatization chemistry that is useful for generating covalently-conjugated therapeutic prodrugs [1]. Fullerene derivatives have been shown to spontaneously form non-covalent Immunoconjugates with antibodies such as the anti-gp240 melanoma antibody ZME-018; a recent study revealed how ZME-018 forms non-covalent Immunoconjugates with C 60 derivatives without significant loss of antibody activity [2]. Endohedral gadofullerene derivatives have been shown in prior studies to function effectively as T 1 -active magnetic resonance imaging (MRI) contrast agents, both for in vivo MRI [3] and for in vitro cellular labeling [4]. In this study, chemical routes for conjugation of paclitaxel and Gd@C 60 are being developed to form a combined therapeutic/imaging agent prodrug. Using the gadofullerene-paclitaxel conjugates, Immunoconjugates with the anti-gp240 melanoma antibody ZME-018 will be tested for cellular uptake, for MR imaging efficacy and for cytotoxicity against melanoma cancer cells in vitro. The strategy of combining antibody targeting with a therapeutic MR imaging agent will improve melanoma diagnosis and treatment, and has the potential for targeting multiple drugs to cancerous cells at the same time to improve patient outcome. Recent progress toward the gadofullerene-paclitaxel Immunoconjugates, including in vitro cell binding and internalization of conjugates with A375 melanoma cells, will be discussed.
Sture Lindegren - One of the best experts on this subject based on the ideXlab platform.
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Labeled Antibodies with an e-Lysyl-3- (Trimethylstannyl)Benzamide Immunoconjugate
2020Co-Authors: Sture Lindegren, Sofia Frost, Elin Haglund, Holger JensenAbstract:211At-labeled tumor-specific antibodies have long been considered for the treatment of disseminated cancer. However, the limited availability of the nuclide and the poor efficacy of labeling procedures at clinical activity levels present major obstacles to their use. This study evaluated a procedure for the direct astatination of antibodies for the production of clinical activity levels. Methods: The monoclonal antibody trastuzumab was conjugated with the reagent N-succinimidyl-3-(trimethylstannyl)benzoate, and the Immunoconjugate was labeled with astatine. Before astatination of the conjugated antibody, the nuclide was activated with N-iodosuccinimide. The labeling reaction was evaluated in terms of reaction time, volume of reaction solvent, Immunoconjugate concentration, and applied activity. The quality of the astatinated antibodies was determined by in vitro analysis and biodistribution studies in nude mice. Results: The reaction proceeded almost instantaneously, and the results indicated a low dependence on Immunoconjugate concentration and applied activity. Radiochemical labeling yields were in the range of 68%281%, and a specific radioactivity of up to 1 GBq/mg could be achieved. Stability and radiochemical purity were equal to or better than those attained with a conventional 2-step procedure. Dissociation constants for directly astatinated, conventionally astatinated, and radioiodinated trastuzumab were 1.0 6 0.06 (mean 6 SD), 0.44 6 0.06, and 0.29 6 0.02 nM, respectively. The tissue distribution in non‐tumor-bearing nude mice revealed only minor differences in organ uptake relative to that obtained with the conventional method. Conclusion: The direct astatination procedure enables the high-yield production of astatinated antibodies with radioactivity in the amounts re
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Synthesis and Evaluation of Astatinated N -[2-(Maleimido)ethyl]-3-(trimethylstannyl)benzamide Immunoconjugates
Bioconjugate Chemistry, 2016Co-Authors: Emma Aneheim, Stig Palm, Holger Jensen, Anders Gustafsson, Per Albertsson, Tom Back, Sofia Svedhem, Sture LindegrenAbstract:Effective treatment of metastasis is a great challenge in the treatment of different types of cancers. Targeted alpha therapy utilizes the short tissue range (50–100 μm) of α particles, making the method suitable for treatment of disseminated occult cancers in the form of microtumors or even single cancer cells. A promising radioactive nuclide for this type of therapy is astatine-211. Astatine-211 attached to tumor-specific antibodies as carrier molecules is a system currently under investigation for use in targeted alpha therapy. In the common radiolabeling procedure, astatine is coupled to the antibody arbitrarily on lysine residues. By instead coupling astatine to disulfide bridges in the antibody structure, the immunoreactivity of the antibody conjugates could possibly be increased. Here, the disulfide-based conjugation was performed using a new coupling reagent, maleimidoethyl 3-(trimethylstannyl)benzamide (MSB), and evaluated for chemical stability in vitro. The Immunoconjugates were subsequently astatinated, resulting in both high radiochemical yield and high specific activity. The MSB-conjugate was shown to be stable with a long shelf life prior to the astatination. In a comparison of the in vivo distribution of the new Immunoconjugate with other tin-based Immunoconjugates in tumor-bearing mice, the MSB conjugation method was found to be a viable option for successful astatine labeling of different monoclonal antibodies.
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Shelf-Life of ɛ-Lysyl-3-(Trimethylstannyl)Benzamide Immunoconjugates, Precursors for 211At Labeling of Antibodies
Cancer Biotherapy and Radiopharmaceuticals, 2015Co-Authors: Emma Aneheim, Holger Jensen, Per Albertsson, Jenny Halleröd, Stellan Holgersson, Sture LindegrenAbstract:Astatine-211 is possibly the most promising radionuclide for targeted alpha-particle therapy when it comes to the treatment of occult disseminated cancer. Preclinical research has proven effective, and patient studies have been initiated based on these results. However, a lack of production capacity and the complex radiochemistry of At-211 are major obstacles for research and prospective clinical applications. In the present study, astatination of Immunoconjugates, already prepared well in advance before radiolabeling, was performed to investigate the possibility of formulating a kit-like reagent for the production of At-211 radiopharmaceuticals. The shelf-life of e-lysyl-3-(trimethylstannyl)benzamide Immunoconjugates was evaluated, that is, the effect of different storage times on the quality of the Immunoconjugates. The quality being referred to is the capacity to maintain a good radiochemical yield and good cell-binding property after labeling with At-211. The stability of the conjugates was found to be pH dependent with high stability at pH >= 7 and less stability at pH
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direct procedure for the production of 211at labeled antibodies with an e lysyl 3 trimethylstannyl benzamide Immunoconjugate
The Journal of Nuclear Medicine, 2008Co-Authors: Sture Lindegren, Sofia Frost, Elin Haglund, Jorgen Elgqvist, Tom Back, Holger JensenAbstract:(211)At-labeled tumor-specific antibodies have long been considered for the treatment of disseminated cancer. However, the limited availability of the nuclide and the poor efficacy of labeling procedures at clinical activity levels present major obstacles to their use. This study evaluated a procedure for the direct astatination of antibodies for the production of clinical activity levels. METHODS: The monoclonal antibody trastuzumab was conjugated with the reagent N-succinimidyl-3-(trimethylstannyl)benzoate, and the Immunoconjugate was labeled with astatine. Before astatination of the conjugated antibody, the nuclide was activated with N-iodosuccinimide. The labeling reaction was evaluated in terms of reaction time, volume of reaction solvent, Immunoconjugate concentration, and applied activity. The quality of the astatinated antibodies was determined by in vitro analysis and biodistribution studies in nude mice. RESULTS: The reaction proceeded almost instantaneously, and the results indicated a low dependence on Immunoconjugate concentration and applied activity. Radiochemical labeling yields were in the range of 68%-81%, and a specific radioactivity of up to 1 GBq/mg could be achieved. Stability and radiochemical purity were equal to or better than those attained with a conventional 2-step procedure. Dissociation constants for directly astatinated, conventionally astatinated, and radioiodinated trastuzumab were 1.0+/-0.06 (mean+/-SD), 0.44+/-0.06, and 0.29+/-0.02 nM, respectively. The tissue distribution in non-tumor-bearing nude mice revealed only minor differences in organ uptake relative to that obtained with the conventional method. CONCLUSION: The direct astatination procedure enables the high-yield production of astatinated antibodies with radioactivity in the amounts required for clinical applications.
Holger Jensen - One of the best experts on this subject based on the ideXlab platform.
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Labeled Antibodies with an e-Lysyl-3- (Trimethylstannyl)Benzamide Immunoconjugate
2020Co-Authors: Sture Lindegren, Sofia Frost, Elin Haglund, Holger JensenAbstract:211At-labeled tumor-specific antibodies have long been considered for the treatment of disseminated cancer. However, the limited availability of the nuclide and the poor efficacy of labeling procedures at clinical activity levels present major obstacles to their use. This study evaluated a procedure for the direct astatination of antibodies for the production of clinical activity levels. Methods: The monoclonal antibody trastuzumab was conjugated with the reagent N-succinimidyl-3-(trimethylstannyl)benzoate, and the Immunoconjugate was labeled with astatine. Before astatination of the conjugated antibody, the nuclide was activated with N-iodosuccinimide. The labeling reaction was evaluated in terms of reaction time, volume of reaction solvent, Immunoconjugate concentration, and applied activity. The quality of the astatinated antibodies was determined by in vitro analysis and biodistribution studies in nude mice. Results: The reaction proceeded almost instantaneously, and the results indicated a low dependence on Immunoconjugate concentration and applied activity. Radiochemical labeling yields were in the range of 68%281%, and a specific radioactivity of up to 1 GBq/mg could be achieved. Stability and radiochemical purity were equal to or better than those attained with a conventional 2-step procedure. Dissociation constants for directly astatinated, conventionally astatinated, and radioiodinated trastuzumab were 1.0 6 0.06 (mean 6 SD), 0.44 6 0.06, and 0.29 6 0.02 nM, respectively. The tissue distribution in non‐tumor-bearing nude mice revealed only minor differences in organ uptake relative to that obtained with the conventional method. Conclusion: The direct astatination procedure enables the high-yield production of astatinated antibodies with radioactivity in the amounts re
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Synthesis and Evaluation of Astatinated N -[2-(Maleimido)ethyl]-3-(trimethylstannyl)benzamide Immunoconjugates
Bioconjugate Chemistry, 2016Co-Authors: Emma Aneheim, Stig Palm, Holger Jensen, Anders Gustafsson, Per Albertsson, Tom Back, Sofia Svedhem, Sture LindegrenAbstract:Effective treatment of metastasis is a great challenge in the treatment of different types of cancers. Targeted alpha therapy utilizes the short tissue range (50–100 μm) of α particles, making the method suitable for treatment of disseminated occult cancers in the form of microtumors or even single cancer cells. A promising radioactive nuclide for this type of therapy is astatine-211. Astatine-211 attached to tumor-specific antibodies as carrier molecules is a system currently under investigation for use in targeted alpha therapy. In the common radiolabeling procedure, astatine is coupled to the antibody arbitrarily on lysine residues. By instead coupling astatine to disulfide bridges in the antibody structure, the immunoreactivity of the antibody conjugates could possibly be increased. Here, the disulfide-based conjugation was performed using a new coupling reagent, maleimidoethyl 3-(trimethylstannyl)benzamide (MSB), and evaluated for chemical stability in vitro. The Immunoconjugates were subsequently astatinated, resulting in both high radiochemical yield and high specific activity. The MSB-conjugate was shown to be stable with a long shelf life prior to the astatination. In a comparison of the in vivo distribution of the new Immunoconjugate with other tin-based Immunoconjugates in tumor-bearing mice, the MSB conjugation method was found to be a viable option for successful astatine labeling of different monoclonal antibodies.
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Shelf-Life of ɛ-Lysyl-3-(Trimethylstannyl)Benzamide Immunoconjugates, Precursors for 211At Labeling of Antibodies
Cancer Biotherapy and Radiopharmaceuticals, 2015Co-Authors: Emma Aneheim, Holger Jensen, Per Albertsson, Jenny Halleröd, Stellan Holgersson, Sture LindegrenAbstract:Astatine-211 is possibly the most promising radionuclide for targeted alpha-particle therapy when it comes to the treatment of occult disseminated cancer. Preclinical research has proven effective, and patient studies have been initiated based on these results. However, a lack of production capacity and the complex radiochemistry of At-211 are major obstacles for research and prospective clinical applications. In the present study, astatination of Immunoconjugates, already prepared well in advance before radiolabeling, was performed to investigate the possibility of formulating a kit-like reagent for the production of At-211 radiopharmaceuticals. The shelf-life of e-lysyl-3-(trimethylstannyl)benzamide Immunoconjugates was evaluated, that is, the effect of different storage times on the quality of the Immunoconjugates. The quality being referred to is the capacity to maintain a good radiochemical yield and good cell-binding property after labeling with At-211. The stability of the conjugates was found to be pH dependent with high stability at pH >= 7 and less stability at pH
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direct procedure for the production of 211at labeled antibodies with an e lysyl 3 trimethylstannyl benzamide Immunoconjugate
The Journal of Nuclear Medicine, 2008Co-Authors: Sture Lindegren, Sofia Frost, Elin Haglund, Jorgen Elgqvist, Tom Back, Holger JensenAbstract:(211)At-labeled tumor-specific antibodies have long been considered for the treatment of disseminated cancer. However, the limited availability of the nuclide and the poor efficacy of labeling procedures at clinical activity levels present major obstacles to their use. This study evaluated a procedure for the direct astatination of antibodies for the production of clinical activity levels. METHODS: The monoclonal antibody trastuzumab was conjugated with the reagent N-succinimidyl-3-(trimethylstannyl)benzoate, and the Immunoconjugate was labeled with astatine. Before astatination of the conjugated antibody, the nuclide was activated with N-iodosuccinimide. The labeling reaction was evaluated in terms of reaction time, volume of reaction solvent, Immunoconjugate concentration, and applied activity. The quality of the astatinated antibodies was determined by in vitro analysis and biodistribution studies in nude mice. RESULTS: The reaction proceeded almost instantaneously, and the results indicated a low dependence on Immunoconjugate concentration and applied activity. Radiochemical labeling yields were in the range of 68%-81%, and a specific radioactivity of up to 1 GBq/mg could be achieved. Stability and radiochemical purity were equal to or better than those attained with a conventional 2-step procedure. Dissociation constants for directly astatinated, conventionally astatinated, and radioiodinated trastuzumab were 1.0+/-0.06 (mean+/-SD), 0.44+/-0.06, and 0.29+/-0.02 nM, respectively. The tissue distribution in non-tumor-bearing nude mice revealed only minor differences in organ uptake relative to that obtained with the conventional method. CONCLUSION: The direct astatination procedure enables the high-yield production of astatinated antibodies with radioactivity in the amounts required for clinical applications.
Maureen Gallant - One of the best experts on this subject based on the ideXlab platform.
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novel doxorubicin monoclonal anti carcinoembryonic antigen antibody Immunoconjugate activity in vitro
Bioorganic & Medicinal Chemistry, 1995Co-Authors: Gervais Berube, Christopher H J Ford, Maureen GallantAbstract:Abstract Doxorubicin was modified with five different heterobifunctional reagents to produce drug analogs containing 3′- N -amide or C-13 hydrazone linkage with maleimide. Synthesis and characterization of two new reagents, 4-maleimidobenzohydrazide trifluoroacetate salt (13) and N -(4-maleimidobenzoyl)-6-aminocaprohydrazide trifluoroacetate salt (14) are described here. All Dox maleimido derivatives were conjugated to thiolated anti-carcinoembryonic antigen monoclonal antibody, 11-285-14, via a Michael addition reaction. Antibody-directed cytotoxicity was demonstrated with the MTT assay using combinations of antigen-positive and antigen-negative cell lines. The Immunoconjugates prepared from Dox 3′- N -amide analogs are not active in vitro , however, Dox(hydrazone-linked) Immunoconjugates are selectively toxic to the CEA positive cell line.
M.g. Rosenblum - One of the best experts on this subject based on the ideXlab platform.
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Cell Internalization Studies of Gadofullerene-(ZME-018) Immunoconjugates into
2020Co-Authors: Christopher Scott Berger, Robert D. Bolskar, John W. Marks, M.g. Rosenblum, Lon J. WilsonAbstract:Fullerene (C60)–monoclonal antibody (mAb) Immunoconjugates have been determined to internalize into target cells using water-soluble Gd 3+ ion–filled metallofullerenes (Gd@C60[OH]x). Two separate conjugations of Gd@C60(OH)x with the antibody ZME-018 and a murine antibody mixture (MuIgG) were performed in a 1:5 mAb/Gd@C60 ratio. Characterization of the Immunoconjugates was established using inductively coupled plasma mass spectrometry (ICP-MS) for Gd 3+ and UV-Vis spectrometry (for Gd@C60 +C 60). Once conjugated, enzyme-linked immunosorbent assays showed little change in the specific binding of ZME-018. Each Immunoconjugate was exposed to two cancer cell lines, A375m (antigen positive), and T24, bladder carcinoma (antigen negative). Internalization levels of the Immunoconjugate were determined at various time points during 24 hours by harvesting and digesting the cells with 70% HNO3 for Gd 3+ ion analysis by ICP-MS. These results are the first to demonstrate the practicality of a targeted cancer therapy based on fullerene immunotherapy.
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Fullerene Immunoconjugates for Cancer Imaging and Treatment
2020Co-Authors: C Scott Berger, Robert D. Bolskar, Lon J. Wilson, M.g. Rosenblum, J. William MarksAbstract:Metallofullerene-paclitaxel-antibody conjugates are under investigation for combined cancer imaging and treatment. Fullerenes are non-toxic carbon cage molecules with a rich derivatization chemistry that is useful for generating covalently-conjugated therapeutic prodrugs [1]. Fullerene derivatives have been shown to spontaneously form non-covalent Immunoconjugates with antibodies such as the anti-gp240 melanoma antibody ZME-018; a recent study revealed how ZME-018 forms non-covalent Immunoconjugates with C60 derivatives without significant loss of antibody activity [2]. Endohedral gadofullerene derivatives have been shown in prior studies to function effectively as T1-active magnetic resonance imaging (MRI) contrast agents, both for in vivo MRI [3] and for in vitro cellular labeling [4].
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Cell Internalization Studies of Gadofullerene-(ZME-018) Immunoconjugates into A375m Melanoma Cells
Translational Oncology, 2011Co-Authors: Christopher Scott Berger, Robert D. Bolskar, John W. Marks, M.g. Rosenblum, Lon J. WilsonAbstract:Abstract Fullerene (C60)-monoclonal antibody (mAb) Immunoconjugates have been determined to internalize into target cells using water-soluble Gd3+ ion-filled metallofullerenes (Gd@C60[OH]x). Two separate conjugations of Gd@C60(OH)x with the antibody ZME-018 and a murine antibody mixture (MuIgG) were performed in a 1:5 mAb/Gd@C60 ratio. Characterization of the Immunoconjugates was established using inductively coupled plasma mass spectrometry (ICP-MS) for Gd3+ and UV-Vis spectrometry (for Gd@C60 + C60). Once conjugated, enzyme-linked immunosorbent assays showed little change in the specific binding of ZME-018. Each Immunoconjugate was exposed to two cancer cell lines, {A375m} (antigen positive), and T24, bladder carcinoma (antigen negative). Internalization levels of the Immunoconjugate were determined at various time points during 24 hours by harvesting and digesting the cells with 70% {HNO3} for Gd3+ ion analysis by ICP-MS. These results are the first to demonstrate the practicality of a targeted cancer therapy based on fullerene immunotherapy.
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Fullerene (C60) Immunoconjugates: interaction of water-soluble C60 derivatives with the murine anti-gp240 melanoma antibody
Chemical Communications, 2006Co-Authors: Jared M. Ashcroft, Dmitri A. Tsyboulski, Tatiana Y. Zakharian, John W. Marks, R. Bruce Weisman, Keith B. Hartman, M.g. Rosenblum, Lon J. WilsonAbstract:The first fullerene (C60) Immunoconjugates have been prepared and characterized as an initial step toward the development of fullerene immunotherapy (FIT).
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Fullerene Immunoconjugates for Cancer Imaging and Treatment
J. Am. Chem. Soc, 2005Co-Authors: C Scott Berger, Jay Collier, Robert D. Bolskar, Lon J. Wilson, M.g. Rosenblum, J William Marks IiiAbstract:The 217 th Meeting of the Electrochemical Society Vancouver, BC Canada – April 25-30, 2010 Metallofullerene-paclitaxel-antibody conjugates are under investigation for combined cancer imaging and treatment. Fullerenes are non-toxic carbon cage molecules with a rich derivatization chemistry that is useful for generating covalently-conjugated therapeutic prodrugs [1]. Fullerene derivatives have been shown to spontaneously form non-covalent Immunoconjugates with antibodies such as the anti-gp240 melanoma antibody ZME-018; a recent study revealed how ZME-018 forms non-covalent Immunoconjugates with C 60 derivatives without significant loss of antibody activity [2]. Endohedral gadofullerene derivatives have been shown in prior studies to function effectively as T 1 -active magnetic resonance imaging (MRI) contrast agents, both for in vivo MRI [3] and for in vitro cellular labeling [4]. In this study, chemical routes for conjugation of paclitaxel and Gd@C 60 are being developed to form a combined therapeutic/imaging agent prodrug. Using the gadofullerene-paclitaxel conjugates, Immunoconjugates with the anti-gp240 melanoma antibody ZME-018 will be tested for cellular uptake, for MR imaging efficacy and for cytotoxicity against melanoma cancer cells in vitro. The strategy of combining antibody targeting with a therapeutic MR imaging agent will improve melanoma diagnosis and treatment, and has the potential for targeting multiple drugs to cancerous cells at the same time to improve patient outcome. Recent progress toward the gadofullerene-paclitaxel Immunoconjugates, including in vitro cell binding and internalization of conjugates with A375 melanoma cells, will be discussed.
