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Radioimmunotherapy

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https://www.readbyqxmd.com/read/29158362/cd38-bispecific-antibody-pretargeted-radioimmunotherapy-for-multiple-myeloma-and-other-b-cell-malignancies
#1
Damian J Green, Shyril O'Steen, Yukang Lin, Melilssa L Comstock, Aimee L Kenoyer, Donald K Hamlin, D Scott Wilbur, Darrell R Fisher, Margaret Nartea, Mark D Hylarides, Ajay K Gopal, Theodore A Gooley, Johnnie J Orozco, Brian G Till, Kelly D Orcutt, K Dane Wittrup, Oliver W Press
Pretargeted radioimmunotherapy (PRIT) has demonstrated remarkable efficacy targeting tumor antigens, but immunogenicity and endogenous biotin blocking may limit clinical translation. We describe a new PRIT approach for the treatment of Multiple Myeloma (MM) and other B cell malignancies, for which we developed an anti-CD38 bispecific fusion protein that eliminates endogenous biotin interference and immunogenic elements. In murine xenograft models of MM and non-Hodgkin lymphoma (NHL), the CD38 bispecific construct demonstrated excellent blood clearance and tumor targeting...
November 20, 2017: Blood
https://www.readbyqxmd.com/read/29129050/metal-free-cycloaddition-chemistry-driven-pretargeted-radioimmunotherapy-using-%C3%AE-particle-radiation
#2
Manan Shah, Xiuli Zhang, Raffaella Rossin, Marc S Robillard, Darrell Fisher, Tyler Bueltmann, Freek J M Hoeben, Thomas Quinn
The pretargeted radioimmunotherapy approach (PRIT) decouples the administration of tumor targeting monoclonal antibodies (mAb) from that of the radiolabeled ligand. This multi-step strategy allows delivery of high doses of radiation to tumor cells while minimizing non-specific normal tissue irradiation. In this study, we evaluated the potential of pretargeted α-particle radioimmunotherapy based on inverse electron demand Diels-Alder reaction (IEDAA) between trans-cyclooctene (TCO) and tetrazine (Tz). Two tetrazine based chelators, DOTA-Tz and TCMC-Tz, were synthesized and compared for their radiolabeling efficiency with 212Pb, radiochemical stability and in-vivo pharmacokinetics...
November 12, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/29097747/antibody-pegylation-in-bioorthogonal-pretargeting-with-trans-cyclooctene-tetrazine-cycloaddition-in-vitro-and-in-vivo-evaluation-in-colorectal-cancer-models
#3
Aurélie Rondon, Nancy Ty, Jean-Baptiste Bequignat, Mercedes Quintana, Arnaud Briat, Tiffany Witkowski, Bernadette Bouchon, Claude Boucheix, Elisabeth Miot-Noirault, Jean-Pierre Pouget, Jean-Michel Chezal, Isabelle Navarro-Teulon, Emmanuel Moreau, Françoise Degoul
Bioorthogonal chemistry represents a challenging approach in pretargeted radioimmunotherapy (PRIT). We focus here on mAb modifications by grafting an increase amount of trans-cyclooctene (TCO) derivatives (0 to 30 equivalents with respect to mAb) bearing different polyethylene glycol (PEG) linkers between mAb and TCO (i.e. PEG0 (1), PEG4 (2) and PEG12 (3)) and assessing their functionality. We used colorectal xenograft (HT29/Ts29.2) and peritoneal carcinomatosis (A431-CEA-Luc/35A7) as tumor cells/mAbs models and fluorescent tetrazines (TZ)...
November 2, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29083933/beyond-dose-using-pretherapy-biomarkers-to-improve-dose-prediction-of-outcomes-for-radioimmunotherapy-of-non-hodgkin-lymphoma
#4
Peter L Roberson, Lauren B Smith, Meredith A Morgan, Matthew J Schipper, Scott J Wilderman, Anca M Avram, Mark S Kaminski, Yuni K Dewaraja
INTRODUCTION: Non-Hodgkin Lymphoma patients respond differently to therapy according to inherent biological variations. Pretherapy biomarkers may improve dose-response prediction. MATERIALS AND METHODS: Hybrid single-photon emission computed tomography (SPECT)/computed tomography (CT) three-dimensional imaging at multiple time points plus follow-up positron emission tomography (PET)/CT or CT at 2 and 6 months post therapy were used to fit tumor response to combined biological effect and cell clearance models from which three biological effect response parameters (radiosensitivity, cold effect sensitivity, and proliferation potential) were determined per patient...
November 2017: Cancer Biotherapy & Radiopharmaceuticals
https://www.readbyqxmd.com/read/29054987/theranostic-radiolabeled-anti-cd20-sdab-for-targeted-radionuclide-therapy-of-non-hodgkin-lymphoma
#5
Ahmet Krasniqi, Matthias D'Huyvetter, Catarina Xavier, Kevin Van der Jeught, Serge Muyldermans, José Van Der Heyden, Tony Lahoutte, Jan Tavernier, Nick Devoogdt
Anti-CD20 radioimmunotherapy is an effective approach for therapy of relapsed or refractory CD20pos lymphomas, but faces limitations due to poor tumor penetration and undesirable pharmacokinetics of full antibodies. Camelid single-domain Ab fragments (sdAbs) might circumvent some of the limitations of radiolabeled full antibodies. In this study, a set of hCD20-targeting sdAbs was generated and their capacity to bind hCD20 was evaluated in vitro and in vivo. A lead sdAb, sdAb 9079, was selected based on its specific tumor targeting and significant lower kidney accumulation compared to other sdAbs...
October 20, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/29033288/the-therapeutic-antibody-lm609-selectively-inhibits-ligand-binding-to-human-%C3%AE-v%C3%AE-3-integrin-via-steric-hindrance
#6
Andrew J Borst, Zachary M James, William N Zagotta, Mark Ginsberg, Felix A Rey, Frank DiMaio, Marija Backovic, David Veesler
The LM609 antibody specifically recognizes αVβ3 integrin and inhibits angiogenesis, bone resorption, and viral infections in an arginine-glycine-aspartate-independent manner. LM609 entered phase II clinical trials for the treatment of several cancers and was also used for αVβ3-targeted radioimmunotherapy. To elucidate the mechanisms of recognition and inhibition of αVβ3 integrin, we solved the structure of the LM609 antigen-binding fragment by X-ray crystallography and determined its binding affinity for αVβ3...
November 7, 2017: Structure
https://www.readbyqxmd.com/read/28979315/development-of-dota-rituximab-to-be-labeled-with-90-y-for-radioimmunotherapy-of-b-cell-non-hodgkin-lymphoma
#7
Fariba Johari Doha, Siyavash Rahmani, Pedram Rikhtechi, Samira Rasaneh, Zahra Sheikholislam, Soraya Shahhosseini
NHL is the most common hematologic cancer in adults. Rituximab is the FDA approved treatment of relapsed or refractory low grade B-cell Non-Hodgkin Lymphoma (NHL). But patients eventually become resistant to rituximab. Since lymphocytes and lymphoma cells are highly radiosensitive, low grade NHL that has relapsed or refractory to standard therapy is treated by RIT in which a beta-emitting radionuclide coupled to anti-CD20 antibody. The association of beta emitter radionuclide to rituximab enhances its therapeutic efficacy...
2017: Iranian Journal of Pharmaceutical Research: IJPR
https://www.readbyqxmd.com/read/28971764/recent-research-trends-on-bismuth-compounds-in-cancer-chemo-and-radiotherapy
#8
Mateusz Kowalik, Joanna Masternak, Barbara Barszcz
The application of coordination chemistry in the light of nanotechnology is a rapidly developing research field in medicine. Bismuth complexes have been widely and willingly used in biomedicine with satisfactory therapeutic effects, mostly in Helicobacter pylori eradication, but also as potential anti-microbial and anti-leishmanial agents. Additionally, in recent years, an application of bismuth-based compounds as potent anticancer drugs has also been studied extensively. Therefore, in this review, we want to highlight a number current problems connected with: (1) characterization of bismuth complexes based on thiosemicarbazone, hydrazone, and dithiocarbamate classes of ligands as potential chemotherapeutics, (2) pioneering research on application of bismuth-based nanoparticles and nanodots for radiosensitization, and (3) research challenges in using bismuth radionuclides in targeted radioimmunotherapy...
October 3, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28951872/monoclonal-antibodies-radiolabeling-with-rhenium-188-for-radioimmunotherapy
#9
REVIEW
Licia Uccelli, Petra Martini, Micol Pasquali, Alessandra Boschi
Rhenium-188, obtained from an alumina-based tungsten-188/rhenium-188 generator, is actually considered a useful candidate for labeling biomolecules such as antibodies, antibody fragments, peptides, and DNAs for radiotherapy. There is a widespread interest in the availability of labeling procedures that allow obtaining (188)Re-labeled radiopharmaceuticals for various therapeutic applications, in particular for the rhenium attachment to tumor-specific monoclonal antibodies (Mo)Abs for immunotherapy. Different approaches have been developed in order to obtain (188)Re-radioimmunoconjugates in high radiochemical purity starting from the generator eluted [(188)Re]ReO4(-)...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28940863/a-phase-ii-study-of-radioimmunotherapy-with-intraventricular-131-i-3f8-for-medulloblastoma
#10
Kim Kramer, Neeta Pandit-Taskar, John L Humm, Pat B Zanzonico, Sofia Haque, Ira J Dunkel, Suzanne L Wolden, Maria Donzelli, Debra A Goldman, Jason S Lewis, Serge K Lyashchenko, Yasmin Khakoo, Jorge A Carrasquillo, Mark M Souweidane, Jeffrey P Greenfield, David Lyden, Kevin D De Braganca, Stephen W Gilheeney, Steven M Larson, Nai-Kong V Cheung
BACKGROUND: High-risk and recurrent medulloblastoma (MB) is associated with significant mortality. The murine monoclonal antibody 3F8 targets the cell-surface disialoganglioside GD2 on MB. We tested the efficacy, toxicity, and dosimetry of compartmental radioimmunotherapy (cRIT) with intraventricular (131) I-labeled 3F8 in patients with MB on a phase II clinical trial. METHODS: Patients with histopathologically confirmed high-risk or recurrent MB were eligible for cRIT...
September 22, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/28928164/immunopet-of-malignant-and-normal-b-cells-with%C3%A2-89-zr-and%C3%A2-124-i-labeled-obinutuzumab-antibody-fragments-reveals-differential-cd20-internalization-in-vivo
#11
Kirstin A Zettlitz, Richard Tavare, Scott M Knowles, Kristopher K Steward, John M Timmerman, Anna M Wu
Purpose: The B-cell antigen CD20 provides a target for antibody-based positron emission tomography (immunoPET). We engineered antibody fragments targeting human CD20 and studied their potential as immunoPET tracers in transgenic mice (huCD20TM) and in a murine lymphoma model expressing human CD20.Experimental Design: Anti-CD20 cys-diabody (cDb) and cys-minibody (cMb) based on rituximab and obinutuzumab (GA101) were radioiodinated and used for immunoPET imaging of a murine lymphoma model. Pairwise comparison of obinutuzumab-based antibody fragments labeled with residualizing ((89)Zr) versus non-residualizing ((124)I) radionuclides by region of interest analysis of serial PET images was conducted both in the murine lymphoma model and in huCD20TM to assess antigen modulation in vivoResults:(124)I-GAcDb and (124)I-GAcMb produced high-contrast immunoPET images of B-cell lymphoma and outperformed the respective rituximab-based tracers...
September 19, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28910150/phase-i-ii-trial-of-anticarcinoembryonic-antigen-radioimmunotherapy-gemcitabine-and-hepatic-arterial-infusion-of-fluorodeoxyuridine-postresection-of-liver-metastasis-for-colorectal-carcinoma
#12
Benjamin Cahan, Lucille Leong, Lawrence Wagman, David Yamauchi, Stephen Shibata, Sharon Wilzcynski, Lawrence E Williams, Paul Yazaki, David Colcher, Paul Frankel, Anna Wu, Andrew Raubitschek, John Shively, Jeffrey Y C Wong
OBJECTIVES: Report the feasibility, toxicities, and long-term results of a Phase I/II trial of (90)Y-labeled anticarcinoembryonic antigen (anti-CEA) (cT84.66) radioimmunotherapy (RIT), gemcitabine, and hepatic arterial infusion (HAI) of fluorodeoxyuridine (FUdR) after maximal hepatic resection of metastatic colorectal cancer to the liver. METHODS: Patients with metastatic colorectal cancer to the liver postresection or ablation to minimum disease were eligible. Each cohort received HAI of FUdR for 14 days on a dose escalation schedule...
September 2017: Cancer Biotherapy & Radiopharmaceuticals
https://www.readbyqxmd.com/read/28906259/radiation-and-immunotherapy-in-high-grade-gliomas-where-do-we-stand
#13
Elizabeth Reznik, Andrew W Smith, Shoshana Taube, Justin Mann, Menachem Z Yondorf, Bhupesh Parashar, A Gabriella Wernicke
High-grade glioma is the most common primary brain tumor, with glioblastoma multiforme (GBM) accounting for 52% of all brain tumors. The current standard of care (SOC) of GBM involves surgery followed by adjuvant fractionated radiotherapy and chemotherapy. However, little progress has been made in extending overall survival, progression-free survival, and quality of life. Attempts to characterize and customize treatment of GBM have led to mitigating the deleterious effects of radiotherapy using hypofractionated radiotherapy, as well as various immunotherapies as a promising strategy for the incurable disease...
September 12, 2017: American Journal of Clinical Oncology
https://www.readbyqxmd.com/read/28893110/radioimmunotherapy-for-delivery-of-cytotoxic-radioisotopes-current-status-and-challenges
#14
Carlos Daniel Martins, Gabriela Kramer-Marek, Wim J G Oyen
Radioimmunotherapy (RIT) with monoclonal antibodies and their fragments labelled with radionuclides emitting α-particles, β-particles or Auger electrons have been used for many years in the development of anticancer strategies. While RIT has resulted in approved radiopharmaceuticals for the treatment of hematological malignancies, its use in solid tumors still remains challenging. Areas covered: In this review, we discuss the exciting progress towards elucidating the potential of current and novel radioimmunoconjugates and address the challenges for translation into clinical practice...
September 12, 2017: Expert Opinion on Drug Delivery
https://www.readbyqxmd.com/read/28869617/a-phase-1-trial-of-90-y-zevalin-radioimmunotherapy-with-autologous-stem-cell-transplant-for-multiple-myeloma
#15
A Dispenzieri, A D'Souza, M A Gertz, K Laumann, G Wiseman, M Q Lacy, B LaPlant, F Buadi, S R Hayman, S K Kumar, D Dingli, W J Hogan, S M Ansell, D A Gastineau, D J Inwards, I N Micallef, L F Porrata, P B Johnston, M R Litzow, T E Witzig
This phase 1 study (clinical trial NCT00477815) was conducted to determine the maximum tolerated dose (MTD) of yttrium-90 ibritumomab tiuxetan ((90)Y-Zevalin) with high dose melphalan (HDM) therapy in multiple myeloma (MM) patients undergoing autologous stem cell transplantation (ASCT). In a 3+3 trial design, 30 patients received rituximab 250 mg/m(2) with indium-111 ibritumomab tiuxetan ((111)In-Zevalin) for dosimetry (day -22); rituximab 250 mg/m(2) with escalating doses of (90)Y-Zevalin (day -14); melphalan 100 mg/m(2) (days -2,-1) followed by ASCT (day 0) and sargramostim (GM-CSF, day 0) until neutrophil engraftment...
October 2017: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/28821931/targeting-angiogenesis-for-radioimmunotherapy-with-a-177-lu-labeled-antibody
#16
Emily B Ehlerding, Saige Lacognata, Dawei Jiang, Carolina A Ferreira, Shreya Goel, Reinier Hernandez, Justin J Jeffery, Charles P Theuer, Weibo Cai
PURPOSE: Increased angiogenesis is a marker of aggressiveness in many cancers. Targeted radionuclide therapy of these cancers with angiogenesis-targeting agents may curtail this increased blood vessel formation and slow the growth of tumors, both primary and metastatic. CD105, or endoglin, has a primary role in angiogenesis in a number of cancers, making this a widely applicable target for targeted radioimmunotherapy. METHODS: The anti-CD105 antibody, TRC105 (TRACON Pharmaceuticals), was conjugated with DTPA for radiolabeling with (177)Lu (t 1/2 6...
August 18, 2017: European Journal of Nuclear Medicine and Molecular Imaging
https://www.readbyqxmd.com/read/28816801/bevacizumab-associated-bowel-microperforation-in-a-patient-with-neuroblastoma
#17
Rachel Glincher, Anita P Price, Michael P LaQuaglia, Brian H Kushner, Shakeel Modak
The antivascular endothelial growth factor antibody, bevacizumab, is effective against several malignancies in adults but unproven in pediatric oncology. In early phase pediatric studies toxicities were similar to those in adults. Bowel perforation in adults is a rare but serious toxicity, but has not been hitherto reported in children. A 5-year-old boy with chemoresistant neuroblastoma treated with bevacizumab plus radioimmunotherapy developed acute abdominal pain. Computed tomography scan showed free abdominal air and pneumatosis coli...
August 14, 2017: Journal of Pediatric Hematology/oncology
https://www.readbyqxmd.com/read/28777832/endless-research-ii-the-genomic-era-neohippocratic-medicine
#18
EDITORIAL
Philip C Grammaticos, Dimitrios E Antoniou
The great progress of genetics research, during 2015-2017, will certainly influence all medical specialties including nuclear medicine. In nuclear medicine there are still problems to solve as to differentiate between infection, inflammation and cancer etc. Furthermore, in dosimetry and radiation protection there are worldwide problems. It has been reported that (64) Cu-cetuximab immune-PET represented EGFR expression levels in ESCC tumors and that (177) Lu-cetuximab radioimmunotherapy effectively inhibited the tumor growth...
May 2017: Hellenic Journal of Nuclear Medicine
https://www.readbyqxmd.com/read/28767228/-89-zr-immuno-positron-emission-tomography-in-oncology-state-of-the-art-89-zr-radiochemistry
#19
REVIEW
Sandra Heskamp, René Raavé, Otto Boerman, Mark Rijpkema, Victor Goncalves, Franck Denat
Immuno-positron emission tomography (immunoPET) with (89)Zr-labeled antibodies has shown great potential in cancer imaging. It can provide important information about the pharmacokinetics and tumor-targeting properties of monoclonal antibodies and may help in anticipating on toxicity. Furthermore, it allows accurate dose planning for individualized radioimmunotherapy and may aid in patient selection and early-response monitoring for targeted therapies. The most commonly used chelator for (89)Zr is desferrioxamine (DFO)...
September 20, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/28745238/effect-of-number-of-bifunctional-chelating-agents-on-the-pharmacokinetics-and-immunoreactivity-of-177lu-labeled-rituximab-a-systemic-study
#20
Mohini Guleria, Tapas Das, Chandan Kumar, Rohit Sharma, Jeyachitra Amirdhanayagam, Haladhar D Sarma, Ashutosh Dash
OBJECTIVE: Monoclonal antibodies (mAbs) have been radiolabeled with a variety of radioisotopes utilizing various kinds of bi-functional chelating agents (BFCAs) with an aim to develop suitable agents for radioimmunotherapy. The number of BFCA moieties present per antibody molecule plays a significant role in determining the pharmacokinetics and immunoreactivity exhibited by the radiolabeled antibodies. The objective of the present study is to evaluate the effect of number of BFCA moieties present per antibody molecule on the pharmacokinetics and immunoreactivity of the 177Lu-labeled Rituximab...
July 25, 2017: Anti-cancer Agents in Medicinal Chemistry
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