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  1. AU="Yazaki, Paul J"
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  1. Artikel: Enhanced Therapeutic Effects of

    Mohajershojai, Tabassom / Spangler, Douglas / Chopra, Saloni / Frejd, Fredrik Y / Yazaki, Paul J / Nestor, Marika

    Cancers

    2023  Band 15, Heft 17

    Abstract: Carcinoembryonic antigen (CEA) has emerged as an attractive target for theranostic applications in colorectal cancers (CRCs). In the present study, the humanized anti-CEA antibody hT84.66-M5A (M5A) was labeled ... ...

    Abstract Carcinoembryonic antigen (CEA) has emerged as an attractive target for theranostic applications in colorectal cancers (CRCs). In the present study, the humanized anti-CEA antibody hT84.66-M5A (M5A) was labeled with
    Sprache Englisch
    Erscheinungsdatum 2023-08-24
    Erscheinungsland Switzerland
    Dokumenttyp Journal Article
    ZDB-ID 2527080-1
    ISSN 2072-6694
    ISSN 2072-6694
    DOI 10.3390/cancers15174239
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  2. Artikel: In Vitro

    Mohajershojai, Tabassom / Jha, Preeti / Boström, Anna / Frejd, Fredrik Y / Yazaki, Paul J / Nestor, Marika

    Frontiers in oncology

    2022  Band 12, Seite(n) 849338

    Abstract: Carcinoembryonic antigen (CEA) is an antigen that is highly expressed in colorectal cancers and widely used as a tumor marker. ...

    Abstract Carcinoembryonic antigen (CEA) is an antigen that is highly expressed in colorectal cancers and widely used as a tumor marker.
    Sprache Englisch
    Erscheinungsdatum 2022-03-31
    Erscheinungsland Switzerland
    Dokumenttyp Journal Article
    ZDB-ID 2649216-7
    ISSN 2234-943X
    ISSN 2234-943X
    DOI 10.3389/fonc.2022.849338
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  3. Artikel ; Online: Improved Tumor Responses with Sequential Targeted α-Particles Followed by Interleukin 2 Immunocytokine Therapies in Treatment of CEA-Positive Breast and Colon Tumors in CEA Transgenic Mice.

    Minnix, Megan / Kujawski, Maciej / Poku, Erasmus / Yazaki, Paul J / Wong, Jeffrey Y / Shively, John E

    Journal of nuclear medicine : official publication, Society of Nuclear Medicine

    2022  Band 63, Heft 12, Seite(n) 1859–1864

    Abstract: Targeted α-therapy (TAT) delivers high-linear-transfer-energy α-particles to tumors with the potential to generate tumor immune responses that may be augmented by antigen-targeted immunotherapy. ...

    Abstract Targeted α-therapy (TAT) delivers high-linear-transfer-energy α-particles to tumors with the potential to generate tumor immune responses that may be augmented by antigen-targeted immunotherapy.
    Mesh-Begriff(e) Animals ; Mice ; Carcinoembryonic Antigen ; Mice, Transgenic ; Interleukin-2 ; Mice, Inbred C57BL ; Colonic Neoplasms/therapy ; Immunotherapy
    Chemische Substanzen Carcinoembryonic Antigen ; Interleukin-2
    Sprache Englisch
    Erscheinungsdatum 2022-06-30
    Erscheinungsland United States
    Dokumenttyp Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 80272-4
    ISSN 1535-5667 ; 0097-9058 ; 0161-5505 ; 0022-3123
    ISSN (online) 1535-5667
    ISSN 0097-9058 ; 0161-5505 ; 0022-3123
    DOI 10.2967/jnumed.122.264126
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  4. Artikel ; Online: Pretargeting with Cucurbituril-Adamantane Host-Guest Pair in Xenograft Models.

    Jallinoja, Vilma I J / Abbriano, Courtney H / Bhatt, Kavita / Kaur, Amritjyot / Schlyer, David J / Yazaki, Paul J / Carney, Brandon D / Houghton, Jacob L

    Journal of nuclear medicine : official publication, Society of Nuclear Medicine

    2023  Band 64, Heft 8, Seite(n) 1203–1209

    Abstract: The goal of reducing the total-body radiation dose of macromolecule-based nuclear medicine with a 2-step pretargeting strategy has been achieved with several pretargeting methodologies in preclinical and clinical settings. However, the lack of modularity, ...

    Abstract The goal of reducing the total-body radiation dose of macromolecule-based nuclear medicine with a 2-step pretargeting strategy has been achieved with several pretargeting methodologies in preclinical and clinical settings. However, the lack of modularity, biocompatibility, and in vivo stability in existing pretargeting agents obstructs their respective platforms' wide clinical use. We hypothesized that host-guest chemistry would provide an optimal pretargeting methodology. A cucurbit[7]uril host and an adamantane guest molecule form a high-affinity host-guest complex (association constant, ∼10
    Mesh-Begriff(e) Male ; Humans ; Animals ; Mice ; Adamantane/chemistry ; Tissue Distribution ; Heterografts ; Antibodies/metabolism
    Chemische Substanzen Adamantane (PJY633525U) ; Antibodies
    Sprache Englisch
    Erscheinungsdatum 2023-04-06
    Erscheinungsland United States
    Dokumenttyp Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 80272-4
    ISSN 1535-5667 ; 0097-9058 ; 0161-5505 ; 0022-3123
    ISSN (online) 1535-5667
    ISSN 0097-9058 ; 0161-5505 ; 0022-3123
    DOI 10.2967/jnumed.122.265008
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  5. Artikel ; Online: Comparison of IL-2-antibody to IL-2-Fc with or without stereotactic radiation therapy in CEA immunocompetent mice with CEA positive tumors.

    Williams, Lindsay / Li, Lin / Yazaki, Paul J / Wong, Patty / Hong, Teresa / Poku, Erasmus K / Hui, Susanta / Ghimire, Hemendra / Shively, John E / Kujawski, Maciej

    Cancer medicine

    2024  Band 13, Heft 3, Seite(n) e6909

    Abstract: Background: The potent immune effects of interleukin-2 (IL-2) for cancer therapy can be increased by genetic fusion of IL-2 to the Fc domain of an antibody (IL-2-Fc) or tumor targeted by genetic fusion to a whole antibody known as an immunocytokine (ICK) ...

    Abstract Background: The potent immune effects of interleukin-2 (IL-2) for cancer therapy can be increased by genetic fusion of IL-2 to the Fc domain of an antibody (IL-2-Fc) or tumor targeted by genetic fusion to a whole antibody known as an immunocytokine (ICK).
    Methods: An anti-CEA ICK (M5A-IL-2) was compared to an IL-2-Fc fusion protein using tumor therapy and PET imaging in CEA transgenic immunocompetent mice bearing CEA positive colon or breast tumors. Combination with stereotactic radiation therapy (SRT) was performed with either ICK or IL-2-Fc.
    Results: ICK and IL-2-Fc had comparable antitumor effects in both tumor models, although ICK had higher tumor uptake and slower blood clearance than an IL-2-Fc. Analysis of IFNγ
    Conclusions: IL-2-Fc had comparable antitumor efficacy to CEA-targeted M5A-IL-2 ICK, while both fusion proteins induced immune memory when combined with SRT. Differences in the therapeutic mechanisms of both agents were observed.
    Mesh-Begriff(e) Mice ; Animals ; Interleukin-2/pharmacology ; CD8-Positive T-Lymphocytes ; Radiosurgery ; Neoplasms/therapy ; Antibodies ; Mice, Transgenic
    Chemische Substanzen Interleukin-2 ; Antibodies
    Sprache Englisch
    Erscheinungsdatum 2024-02-05
    Erscheinungsland United States
    Dokumenttyp Journal Article
    ZDB-ID 2659751-2
    ISSN 2045-7634 ; 2045-7634
    ISSN (online) 2045-7634
    ISSN 2045-7634
    DOI 10.1002/cam4.6909
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  6. Artikel ; Online: T-cell surface generation of dual bivalent, bispecific T-cell engaging, RNA duplex cross-linked antibodies (dbBiTERs) for re-directed tumor cell lysis.

    Kujawski, Maciej / Li, Lin / Li, Harry / Yazaki, Paul J / Swiderski, Piotr / Shively, John E

    Biotechnology journal

    2021  Band 17, Heft 2, Seite(n) e2100389

    Abstract: Background: Genetic engineered Bispecific T-cell engagers (BiTEs) generate potent cytotoxic effects.: Methods: Alternately, click chemistry engineered, dual specific bivalent Bispecific T-cell engaging antibodies (dbBiTEs) on T-cell surfaces can be ... ...

    Abstract Background: Genetic engineered Bispecific T-cell engagers (BiTEs) generate potent cytotoxic effects.
    Methods: Alternately, click chemistry engineered, dual specific bivalent Bispecific T-cell engaging antibodies (dbBiTEs) on T-cell surfaces can be generated from parent monoclonal antibodies.
    Results: We show the formation of dbBiTEs on the surface of T-cells along with the introduction of complementary 2'-OMe RNA 32-mer oligonucleotides allowing duplex formation between antibodies, designated as dbBiTERs. dbBiTERs generated in solution from anti-CEA and anti-CD3 OKT3 antibodies retained specific binding to CEA positive versus CEA negative cancer cells and to CD3 positive T-cells comparable to dbBiTEs. When T-cells were precoated with dbBiTEs or dbBiTERs and mixed with CEA positive versus CEA negative cancer cells, similar dose dependent and specific cytotoxicity were observed in redirected cell lysis assays. On-cell generated dbBiTERs exerted potent cytotoxic responses against CEA positive targets and were localized at the cell surface by immuno-gold EM. In addition, we demonstrate that target and T-cells, each coated separately with complementary 2'OMe-RNA-linked antibodies can be cross-linked by RNA duplex formation in vitro to generate redirected cell lysis.
    Conclusion: The facile generation of dbBiTERs with specific cytolytic activity from intact antibodies and their generation on-cell offers a new avenue for antigen specific T-cell therapy.
    Mesh-Begriff(e) Antibodies, Bispecific ; CD3 Complex/genetics ; Carcinoembryonic Antigen/genetics ; RNA/genetics ; T-Lymphocytes
    Chemische Substanzen Antibodies, Bispecific ; CD3 Complex ; Carcinoembryonic Antigen ; RNA (63231-63-0)
    Sprache Englisch
    Erscheinungsdatum 2021-11-25
    Erscheinungsland Germany
    Dokumenttyp Journal Article
    ZDB-ID 2221885-3
    ISSN 1860-7314 ; 1860-6768
    ISSN (online) 1860-7314
    ISSN 1860-6768
    DOI 10.1002/biot.202100389
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  7. Artikel ; Online: Investigation of Copper-64-Based Host-Guest Chemistry Pretargeted Positron Emission Tomography.

    Jallinoja, Vilma I J / Carney, Brandon D / Bhatt, Kavita / Abbriano, Courtney H / Schlyer, David J / Yazaki, Paul J / Houghton, Jacob L

    Molecular pharmaceutics

    2022  Band 19, Heft 7, Seite(n) 2268–2278

    Abstract: Pretargeting is a technique that uses macromolecules as targeting agents for nuclear imaging and therapy with the goal of reducing the radiation toxicity to healthy tissues often associated with directly radiolabeled macromolecules. In pretargeting, a ... ...

    Abstract Pretargeting is a technique that uses macromolecules as targeting agents for nuclear imaging and therapy with the goal of reducing the radiation toxicity to healthy tissues often associated with directly radiolabeled macromolecules. In pretargeting, a macromolecule is radiolabeled
    Mesh-Begriff(e) Animals ; Antibodies, Monoclonal/chemistry ; Cell Line, Tumor ; Copper Radioisotopes/chemistry ; Humans ; Immunoconjugates/pharmacokinetics ; Metallocenes ; Mice ; Positron-Emission Tomography/methods
    Chemische Substanzen Antibodies, Monoclonal ; Copper Radioisotopes ; Immunoconjugates ; Metallocenes
    Sprache Englisch
    Erscheinungsdatum 2022-06-14
    Erscheinungsland United States
    Dokumenttyp Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 2138405-8
    ISSN 1543-8392 ; 1543-8384
    ISSN (online) 1543-8392
    ISSN 1543-8384
    DOI 10.1021/acs.molpharmaceut.2c00102
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  8. Artikel ; Online: Multimodality PET and Near-Infrared Fluorescence Intraoperative Imaging of CEA-Positive Colorectal Cancer.

    Lwin, Thinzar M / Minnix, Megan / Li, Lin / Sherman, Anakim / Hong, Teresa / Wong, Jeffery Y C / Olafsen, Tove / Poku, Erasmus / Bouvet, Michael / Fong, Yuman / Shively, John E / Yazaki, Paul J

    Molecular imaging and biology

    2023  Band 25, Heft 4, Seite(n) 727–734

    Abstract: Purpose: Molecular imaging is a major diagnostic component for cancer management, enabling detection, staging of disease, targeting therapy, and monitoring the therapeutic response. The coordination of multimodality imaging techniques further enhances ... ...

    Abstract Purpose: Molecular imaging is a major diagnostic component for cancer management, enabling detection, staging of disease, targeting therapy, and monitoring the therapeutic response. The coordination of multimodality imaging techniques further enhances tumor localization. The development of a single agent for real-time non-invasive targeted positron emission tomography (PET) imaging and fluorescence guided surgery (FGS) will provide the next generation tool in the surgical management of cancer.
    Procedures: The humanized anti-CEA M5A-IR800 "sidewinder" (M5A-IR800-SW) antibody-dye conjugate was designed with a NIR 800 nm dye incorporated into a PEGylated linker and conjugated with the metal chelate p-SCN-Bn-deferoxamine (DFO) for zirconium-89 PET imaging (
    Results: The
    Conclusions: This study demonstrates the potential of a pegylated anti-CEA M5A-IR800-Sidewinder for NIR fluorescence/PET/MR multimodality imaging for intraoperative fluorescence guided surgery.
    Mesh-Begriff(e) Humans ; Mice ; Animals ; Tissue Distribution ; Positron-Emission Tomography/methods ; Immunoconjugates ; Disease Models, Animal ; Cell Line, Tumor ; Zirconium ; Colorectal Neoplasms/diagnostic imaging ; Colorectal Neoplasms/pathology ; Polyethylene Glycols
    Chemische Substanzen Immunoconjugates ; Zirconium (C6V6S92N3C) ; Polyethylene Glycols (3WJQ0SDW1A)
    Sprache Englisch
    Erscheinungsdatum 2023-06-21
    Erscheinungsland United States
    Dokumenttyp Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 2079160-4
    ISSN 1860-2002 ; 1536-1632
    ISSN (online) 1860-2002
    ISSN 1536-1632
    DOI 10.1007/s11307-023-01831-8
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  9. Artikel ; Online: Humanized Anti-Carcinoembryonic Antigen Antibodies Brightly Target and Label Gastric Cancer in Orthotopic Mouse Models.

    Cox, Kristin E / Turner, Michael A / Amirfakhri, Siamak / Lwin, Thinzar M / Hosseini, Mojgan / Ghosh, Pradipta / Obonyo, Marygorret / Murakami, Takashi / Hoffman, Robert M / Yazaki, Paul J / Bouvet, Michael

    The Journal of surgical research

    2023  Band 293, Seite(n) 701–708

    Abstract: Introduction: Gastric cancer poses a major therapeutic challenge. Improved visualization of tumor margins at the time of gastrectomy with fluorescent tumor-specific antibodies could improve outcomes. The present report demonstrates the potential of ... ...

    Abstract Introduction: Gastric cancer poses a major therapeutic challenge. Improved visualization of tumor margins at the time of gastrectomy with fluorescent tumor-specific antibodies could improve outcomes. The present report demonstrates the potential of targeting gastric cancer with a humanized anti-carcinoembryonic antigen (CEA) antibody in orthotopic mouse models.
    Methods: MKN45 cells were injected subcutaneously into nude mice to establish xenograft models. Tumor fragments collected from subcutaneous models were then implanted into the greater curvature of the stomach to establish orthotopic models. For tumor labeling, a humanized anti-CEA antibody (M5A) and IgG as a control, were conjugated with the near-infrared dye IRDye800CW. Time (24-72 h) and dose (50-100 μg) response curves were performed in subcutaneous models. Orthotopic models received 50 μg of M5A-IR800 or 50 μg IgG-IR800 as a control and were imaged after 72 h. Fluorescence imaging was performed on the mice using the LI-COR Pearl Imaging System.
    Results: In subcutaneous models, tumor to background ratios (TBRs) reached 8.85 at 72 h. Median TBRs of orthotopic model primary tumors were 6.25 (interquartile range [IQR] 6.03-7.12) for M5A-IR800 compared to 0.42 (IQR 0.38-0.54) for control. Abdominal wall metastasis median TBRs were 13.52 (IQR 12.79-13.76) for M5A-IR800 and 3.19 (IQR 2.65-3.73) for the control. Immunohistochemistry confirmed CEA expression within tumors.
    Conclusions: Humanized anti-CEA antibodies conjugated to near-infrared dyes provide specific labeling of gastric cancers in mouse models. Orthotopic models demonstrated bright and specific labeling with TBRs greater than ten times that of control. This tumor-specific fluorescent antibody is a promising potential clinical tool for improving visualization of gastric cancer margins at time of surgical resection.
    Mesh-Begriff(e) Humans ; Animals ; Mice ; Stomach Neoplasms ; Mice, Nude ; Carcinoembryonic Antigen ; Antibodies, Monoclonal ; Disease Models, Animal ; Immunoglobulin G ; Fluorescent Dyes ; Cell Line, Tumor
    Chemische Substanzen Carcinoembryonic Antigen ; Antibodies, Monoclonal ; Immunoglobulin G ; Fluorescent Dyes
    Sprache Englisch
    Erscheinungsdatum 2023-10-14
    Erscheinungsland United States
    Dokumenttyp Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, Non-U.S. Gov't
    ZDB-ID 80170-7
    ISSN 1095-8673 ; 0022-4804
    ISSN (online) 1095-8673
    ISSN 0022-4804
    DOI 10.1016/j.jss.2023.08.038
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  10. Artikel ; Online: PEGylated Fluorescent Anti-carcinoembryonic Antigen Antibody Labels Colorectal Cancer Tumors in Orthotopic Mouse Models.

    Turner, Michael A / Amirfakhri, Siamak / Nishino, Hiroto / Neel, Nicholas C / Hosseini, Mojgan / Cox, Kristin E / Lwin, Thinzar M / Li, Lin / Hong, Teresa / Sherman, Anakim / Shively, John E / Hoffman, Robert M / Yazaki, Paul J / Bouvet, Michael

    The Journal of surgical research

    2023  Band 291, Seite(n) 596–602

    Abstract: Introduction: Colorectal cancer (CRC) patients often develop liver metastasis. However, curative resection of liver metastasis is not always possible due to poor visualization of tumor margins. The present study reports the characterization of a ... ...

    Abstract Introduction: Colorectal cancer (CRC) patients often develop liver metastasis. However, curative resection of liver metastasis is not always possible due to poor visualization of tumor margins. The present study reports the characterization of a humanized anti-carcinoembryonic antigen monoclonal antibody conjugated to a PEGylated near-infrared dye, that targets and brightly labels human CRC tumors in metastatic orthotopic mouse models.
    Methods: The hT84.66-M5A (M5A) monoclonal antibody was conjugated with a polyethylene glycol (PEG) chain that incorporated a near infrared (NIR) IR800 dye to establish M5A-IR800 Sidewinder (M5A-IR800-SW). Nude mice with CRC orthotopic primary tumors and liver metastasis both developed from a human CRC cell line, were injected with M5A-IR800-SW and imaged with the Pearl Trilogy Imaging System.
    Results: M5A-IR800-SW targeted and brightly labeled CRC tumors, both in primary-tumor and liver-metastasis models. M5A-IR800-SW at 75 μg exhibited highly-specific tumor labeling in a primary-tumor orthotopic model with a median tumor-to-background ratio of 9.77 and in a liver-metastasis orthotopic model with a median tumor-to-background ratio of 7.23 at 96 h. The precise labeling of the liver metastasis was due to lack of hepatic accumulation of M5A-IR800-SW in the liver.
    Conclusions: M5A-IR800-SW provided bright and targeted NIR images of human CRC in orthotopic primary-tumor and liver-metastasis mouse models. The results of the present study suggest the clinical potential of M5A-IR800-SW for fluorescence-guided surgery including metastasectomies for CRC. The lack of hepatic NIR signal is of critical importance to allow for precise labeling of liver tumors.
    Mesh-Begriff(e) Animals ; Mice ; Humans ; Mice, Nude ; Fluorescent Dyes ; Colorectal Neoplasms/pathology ; Antibodies, Monoclonal ; Liver Neoplasms/diagnosis ; Liver Neoplasms/surgery ; Liver Neoplasms/secondary ; Polyethylene Glycols ; Cell Line, Tumor
    Chemische Substanzen Fluorescent Dyes ; Antibodies, Monoclonal ; Polyethylene Glycols (3WJQ0SDW1A)
    Sprache Englisch
    Erscheinungsdatum 2023-08-02
    Erscheinungsland United States
    Dokumenttyp Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 80170-7
    ISSN 1095-8673 ; 0022-4804
    ISSN (online) 1095-8673
    ISSN 0022-4804
    DOI 10.1016/j.jss.2023.06.013
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