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Immuno-PET Monitoring of Lymphocytes Using the CD8-Specific Antibody REGN5054.
Tavaré, Richard; Danton, Makenzie; Giurleo, Jason T; Makonnen, Sosina; Hickey, Carlos; Arnold, Tomas C; Kelly, Marcus P; Fredriksson, Fanny; Bruestle, Karina; Hermann, Aynur; Ullman, Erica; Edelmann, Kurt H; Potocky, Terra; Dudgeon, Drew; Bhatt, Nikunj B; Doubrovin, Mikhail; Barry, Thomas; Kyratsous, Christos A; Gurer, Cagan; Tu, Naxin; Gartner, Hans; Murphy, Andrew; Macdonald, Lynn E; Popke, Jon; Mintz, Akiva; Griesemer, Adam; Olson, William C; Thurston, Gavin; Ma, Dangshe; Kirshner, Jessica R.
Afiliación
  • Tavaré R; Regeneron Pharmaceuticals Inc., Tarrytown, New York.
  • Danton M; Regeneron Pharmaceuticals Inc., Tarrytown, New York.
  • Giurleo JT; Regeneron Pharmaceuticals Inc., Tarrytown, New York.
  • Makonnen S; Regeneron Pharmaceuticals Inc., Tarrytown, New York.
  • Hickey C; Regeneron Pharmaceuticals Inc., Tarrytown, New York.
  • Arnold TC; Regeneron Pharmaceuticals Inc., Tarrytown, New York.
  • Kelly MP; Regeneron Pharmaceuticals Inc., Tarrytown, New York.
  • Fredriksson F; Columbia Center for Translational Immunology, Department of Medicine, Columbia University Medical Center, New York, New York.
  • Bruestle K; Department of Surgery, Columbia University Medical Center, New York, New York.
  • Hermann A; Columbia Center for Translational Immunology, Department of Medicine, Columbia University Medical Center, New York, New York.
  • Ullman E; Department of Surgery, Columbia University Medical Center, New York, New York.
  • Edelmann KH; Regeneron Pharmaceuticals Inc., Tarrytown, New York.
  • Potocky T; Regeneron Pharmaceuticals Inc., Tarrytown, New York.
  • Dudgeon D; Regeneron Pharmaceuticals Inc., Tarrytown, New York.
  • Bhatt NB; Regeneron Pharmaceuticals Inc., Tarrytown, New York.
  • Doubrovin M; Regeneron Pharmaceuticals Inc., Tarrytown, New York.
  • Barry T; Columbia University PET Center, Department of Radiology, Columbia University Medical Center, New York, New York.
  • Kyratsous CA; Columbia University PET Center, Department of Radiology, Columbia University Medical Center, New York, New York.
  • Gurer C; Regeneron Pharmaceuticals Inc., Tarrytown, New York.
  • Tu N; Regeneron Pharmaceuticals Inc., Tarrytown, New York.
  • Gartner H; Regeneron Pharmaceuticals Inc., Tarrytown, New York.
  • Murphy A; Regeneron Pharmaceuticals Inc., Tarrytown, New York.
  • Macdonald LE; Regeneron Pharmaceuticals Inc., Tarrytown, New York.
  • Popke J; Regeneron Pharmaceuticals Inc., Tarrytown, New York.
  • Mintz A; Regeneron Pharmaceuticals Inc., Tarrytown, New York.
  • Griesemer A; Regeneron Pharmaceuticals Inc., Tarrytown, New York.
  • Olson WC; Columbia University PET Center, Department of Radiology, Columbia University Medical Center, New York, New York.
  • Thurston G; Columbia Center for Translational Immunology, Department of Medicine, Columbia University Medical Center, New York, New York.
  • Ma D; Department of Surgery, Columbia University Medical Center, New York, New York.
  • Kirshner JR; Regeneron Pharmaceuticals Inc., Tarrytown, New York.
Cancer Immunol Res ; 10(10): 1190-1209, 2022 10 04.
Article en En | MEDLINE | ID: mdl-35895745
Assessment of immune-cell subsets within the tumor immune microenvironment is a powerful approach to better understand cancer immunotherapy responses. However, the use of biopsies to assess the tumor immune microenvironment poses challenges, including the potential for sampling error, restricted sampling over time, and inaccessibility of some tissues/organs, as well as the fact that single biopsy analyses do not reflect discordance across multiple intrapatient tumor lesions. Immuno-positron emission tomography (PET) presents a promising translational imaging approach to address the limitations and assess changes in the tumor microenvironment. We have developed 89Zr-DFO-REGN5054, a fully human CD8A-specific antibody conjugate, to assess CD8+ tumor-infiltrating lymphocytes (TIL) pre- and posttherapy. We used multiple assays, including in vitro T-cell activation, proliferation, and cytokine production, and in vivo viral clearance and CD8 receptor occupancy, to demonstrate that REGN5054 has minimal impact on T-cell activity. Preclinical immuno-PET studies demonstrated that 89Zr-DFO-REGN5054 specifically detected CD8+ T cells in lymphoid tissues of CD8-genetically humanized immunocompetent mice (VelociT mice) and discerned therapy-induced changes in CD8+ TILs in two models of response to a CD20xCD3 T-cell activating bispecific antibody (REGN1979, odronextamab). Toxicology studies in cynomolgus monkeys showed no overt toxicity, and immuno-PET imaging in cynomolgus monkeys demonstrated dose-dependent clearance and specific targeting to lymphoid tissues. This work supports the clinical investigation of 89Zr-DFO-REGN5054 to monitor T-cell responses in patients undergoing cancer immunotherapy.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Anticuerpos Biespecíficos / Neoplasias Límite: Animals / Humans Idioma: En Revista: Cancer Immunol Res Año: 2022 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Anticuerpos Biespecíficos / Neoplasias Límite: Animals / Humans Idioma: En Revista: Cancer Immunol Res Año: 2022 Tipo del documento: Article Pais de publicación: Estados Unidos