Astatine-211 conjugated to an anti-CD20 monoclonal antibody eradicates disseminated B-cell lymphoma in a mouse model

Green, Damian J.; Shadman, Mazyar; Jones, Jon C.; Frayo, Shani L.; Kenoyer, Aimee L.; Hylarides, Mark D.; Hamlin, Donald K.; Wilbur, D. Scott; Balkan, Ethan R.; Lin, Yukang; Miller, Brian W.; Frost, Sofia H.L.; Gopal, Ajay K.; Orozco, Johnnie J.; Gooley, Theodore A.; Laird, Kelly; Till, Brian G.; Bäck, Tom; Sandmaier, Brenda M.; Pagel, John M.; Press, Oliver W.

doi:10.1182/blood-2014-11-612770

Cited by 58 publications

(43 citation statements)

References 43 publications

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“…The trend for a decreasing ratio of CD20 + cells compared with CD3 + cells occurs as T cells complete their long developmental process in the thymus and begin to migrate into the periphery beginning around week 14 post-engraftment. For testing ACI-mediated strategies against B cell epitopes, it is possible to inject bioluminescent tumor lines expressing these epitopes into these mice to assay for functionality of infused CAR T cells 39, 40…”

Section: Discussionmentioning

confidence: 99%

In Vivo Murine-Matured Human CD3 + Cells as a Preclinical Model for T Cell-Based Immunotherapies

Haworth

Ironside

Norgaard

et al. 2017

Molecular Therapy - Methods & Clinical Development

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Adoptive cellular immunotherapy is a promising and powerful method for the treatment of a broad range of malignant and infectious diseases. Although the concept of cellular immunotherapy was originally proposed in the 1990s, it has not seen successful clinical application until recent years. Despite significant progress in creating engineered receptors against both malignant and viral epitopes, no efficient preclinical animal models exist for rapidly testing and directly comparing these engineered receptors. The use of matured human T cells in mice usually leads to graft-versus-host disease (GvHD), which severely limits the effectiveness of such studies. Alternatively, adult apheresis CD34+ cells engraft in neonatal non-obese diabetic (NOD)-severe combined immunodeficiency (SCID)-common γ chain–/– (NSG) mice and lead to the development of CD3+ T cells in peripheral circulation. We demonstrate that these in vivo murine-matured autologous CD3+ T cells from humans (MATCH) can be collected from the mice, engineered with lentiviral vectors, reinfused into the mice, and detected in multiple lymphoid compartments at stable levels over 50 days after injection. Unlike autologous CD3+ cells collected from human donors, these MATCH mice did not exhibit GvHD after T cell administration. This novel mouse model offers the opportunity to screen different immunotherapy-based treatments in a preclinical setting.

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Section: Discussionmentioning

confidence: 99%

In Vivo Murine-Matured Human CD3 + Cells as a Preclinical Model for T Cell-Based Immunotherapies

Haworth

Ironside

Norgaard

et al. 2017

Molecular Therapy - Methods & Clinical Development

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“…We have recently shown that parallel bispecific antibodies targeting CD38 on myeloma cells or CD45 on AML cells work as well as the CD20 antibodies published in Cancer Research(15) (and unpublished data, Green and Press). We are currently scaling up production of the bispecific antibodies for human clinical trials.…”

Section: Introductionmentioning

confidence: 80%

“…These beta-particle emitting radionuclides are readily available, have favorable emission characteristics, and are stably retained on antibodies using simple radiolabeling methods(10). Recently, the increased availability of α–emitter radionuclides, in conjunction with advances in radiochemistry leading to radiolabeling platforms capable of providing critical stability to α–particle-labeled biomolecules,(12) has led to promising results using α–emitter RIT in leukemia(13,14), lymphoma (15) and MM (Green and Press unpublished observations). Based on their physical characteristics, α-emitters may be particularly efficacious in minimal residual disease (MRD) settings, where isolated cells and small tumor clusters prevail.…”

Section: Introductionmentioning

confidence: 99%

Whither Radioimmunotherapy: To Be or Not To Be?

Green

Press

2017

Cancer Research

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Therapy of cancer with radiolabeled monoclonal antibodies has produced impressive results in preclinical experiments and in clinical trials conducted in radiosensitive malignancies, particularly B cell lymphomas. Two “first generation”, directly radiolabeled anti-CD20 antibodies, 131Iodine-tositumomab and 90Yttrium-ibritumomab tiuxetan were FDA-approved more than a decade ago, but have been little utilized due to a variety of medical, financial, and logistic obstacles. Newer technologies employing multi-step “pretargeting” methods, particularly those utilizing bispecific antibodies, have greatly enhanced the therapeutic efficacy of radioimmunotherapy (RIT) and diminished its toxicities. The dramatically improved therapeutic index of bispecific antibody pretargeting appears to be sufficiently compelling to justify human clinical trials and reinvigorate enthusiasm for RIT in the treatment of malignancies, particularly lymphomas.

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“…First successful cancer treatment experiments in an animal model with astatine‐boron‐cage‐labelled antibodies were reported by Green et al…”

Section: Investigations Of Astatinated Organic Compoundsmentioning

confidence: 99%

Astatine

Meyer

2018

Labelled Comp Radiopharmac

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This educational review describes and summarizes the historic discovery of element 85, the experiments leading to its physical and chemical characterization and comparison with its lighter homologue iodine. The half-lives of its longest living isotopes At and At with 8.3 and 7.22 hours respectively together with their alpha decay characteristics made these isotopes interesting for radiation biological research. However, the lack of stable isotopes of astatine presents a strong challenge for all characterizations. Nevertheless, the decay characteristics especially of At stimulated several research groups to develop labelling strategies for the preparation of astatinated radiopharmaceuticals for targeted alpha radiation therapy. Because of the distinct differences in the chemical behaviour of astatine, when compared with iodine, these approaches are quite challenging. Accordingly, quite different labelling strategies have been tested, namely nucleophilic and electrophilic substitution reactions as well as complex forming strategies. Classic and new developments for the preparation of these compounds are reviewed.

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Astatine-211 conjugated to an anti-CD20 monoclonal antibody eradicates disseminated B-cell lymphoma in a mouse model

Cited by 58 publications

References 43 publications

In Vivo Murine-Matured Human CD3 + Cells as a Preclinical Model for T Cell-Based Immunotherapies

In Vivo Murine-Matured Human CD3 + Cells as a Preclinical Model for T Cell-Based Immunotherapies

Whither Radioimmunotherapy: To Be or Not To Be?

Astatine

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