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Anti-GD2 synergizes with CD47 blockade to mediate tumor eradication.
Theruvath, Johanna; Menard, Marie; Smith, Benjamin A H; Linde, Miles H; Coles, Garry L; Dalton, Guillermo Nicolas; Wu, Wei; Kiru, Louise; Delaidelli, Alberto; Sotillo, Elena; Silberstein, John L; Geraghty, Anna C; Banuelos, Allison; Radosevich, Molly Thomas; Dhingra, Shaurya; Heitzeneder, Sabine; Tousley, Aidan; Lattin, John; Xu, Peng; Huang, Jing; Nasholm, Nicole; He, Andy; Kuo, Tracy C; Sangalang, Emma R B; Pons, Jaume; Barkal, Amira; Brewer, Rachel E; Marjon, Kristopher D; Vilches-Moure, Jose G; Marshall, Payton L; Fernandes, Ricardo; Monje, Michelle; Cochran, Jennifer R; Sorensen, Poul H; Daldrup-Link, Heike E; Weissman, Irving L; Sage, Julien; Majeti, Ravindra; Bertozzi, Carolyn R; Weiss, William A; Mackall, Crystal L; Majzner, Robbie G.
Afiliación
  • Theruvath J; Department of Pediatrics, Stanford University School of Medicine, Stanford, CA, USA.
  • Menard M; Departments of Neurology, Pediatrics, and Neurological Surgery, Brain Tumor Research Center, University of California, San Francisco, San Francisco, CA, USA.
  • Smith BAH; ChEM-H Institute, Stanford University, Stanford, CA, USA.
  • Linde MH; Department of Chemical & Systems Biology, Stanford University, Stanford, CA, USA.
  • Coles GL; Immunology Graduate Program, Stanford University School of Medicine, Stanford, CA, USA.
  • Dalton GN; Institute for Stem Cell Biology and Regenerative Medicine, Stanford, CA, USA.
  • Wu W; Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA, USA.
  • Kiru L; Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA.
  • Delaidelli A; Department of Pediatrics, Stanford University School of Medicine, Stanford, CA, USA.
  • Sotillo E; Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA, USA.
  • Silberstein JL; Department of Pediatrics, Stanford University School of Medicine, Stanford, CA, USA.
  • Geraghty AC; Department of Radiology, Stanford University School of Medicine, Stanford, CA, USA.
  • Banuelos A; Department of Radiology, Stanford University School of Medicine, Stanford, CA, USA.
  • Radosevich MT; British Columbia Cancer Agency, Vancouver, BC, Canada.
  • Dhingra S; Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA, USA.
  • Heitzeneder S; Immunology Graduate Program, Stanford University School of Medicine, Stanford, CA, USA.
  • Tousley A; Department of Bioengineering, Stanford University Schools of Engineering and Medicine, Stanford, CA, USA.
  • Lattin J; Department of Neurology and Neurological Sciences, Stanford University, Stanford, CA, USA.
  • Xu P; Institute for Stem Cell Biology and Regenerative Medicine, Stanford, CA, USA.
  • Huang J; Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA, USA.
  • Nasholm N; Department of Pediatrics, Stanford University School of Medicine, Stanford, CA, USA.
  • He A; Department of Pediatrics, Stanford University School of Medicine, Stanford, CA, USA.
  • Kuo TC; Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA, USA.
  • Sangalang ERB; Department of Pediatrics, Stanford University School of Medicine, Stanford, CA, USA.
  • Pons J; Department of Pediatrics, Stanford University School of Medicine, Stanford, CA, USA.
  • Barkal A; Department of Pediatrics, Stanford University School of Medicine, Stanford, CA, USA.
  • Brewer RE; Department of Pediatrics, Stanford University School of Medicine, Stanford, CA, USA.
  • Marjon KD; Departments of Neurology, Pediatrics, and Neurological Surgery, Brain Tumor Research Center, University of California, San Francisco, San Francisco, CA, USA.
  • Vilches-Moure JG; Department of Pediatrics, Stanford University School of Medicine, Stanford, CA, USA.
  • Marshall PL; ALX Oncology, Burlingame, CA, USA.
  • Fernandes R; ALX Oncology, Burlingame, CA, USA.
  • Monje M; ALX Oncology, Burlingame, CA, USA.
  • Cochran JR; Institute for Stem Cell Biology and Regenerative Medicine, Stanford, CA, USA.
  • Sorensen PH; Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA, USA.
  • Daldrup-Link HE; Ludwig Center for Cancer Stem Cell Research and Medicine, Stanford University School of Medicine, Stanford, CA, USA.
  • Weissman IL; Stanford Medical Scientist Training Program, Stanford University, Stanford, CA, USA.
  • Sage J; Institute for Stem Cell Biology and Regenerative Medicine, Stanford, CA, USA.
  • Majeti R; Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA, USA.
  • Bertozzi CR; Ludwig Center for Cancer Stem Cell Research and Medicine, Stanford University School of Medicine, Stanford, CA, USA.
  • Weiss WA; Institute for Stem Cell Biology and Regenerative Medicine, Stanford, CA, USA.
  • Mackall CL; Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA, USA.
  • Majzner RG; Ludwig Center for Cancer Stem Cell Research and Medicine, Stanford University School of Medicine, Stanford, CA, USA.
Nat Med ; 28(2): 333-344, 2022 02.
Article en En | MEDLINE | ID: mdl-35027753
ABSTRACT
The disialoganglioside GD2 is overexpressed on several solid tumors, and monoclonal antibodies targeting GD2 have substantially improved outcomes for children with high-risk neuroblastoma. However, approximately 40% of patients with neuroblastoma still relapse, and anti-GD2 has not mediated significant clinical activity in any other GD2+ malignancy. Macrophages are important mediators of anti-tumor immunity, but tumors resist macrophage phagocytosis through expression of the checkpoint molecule CD47, a so-called 'Don't eat me' signal. In this study, we establish potent synergy for the combination of anti-GD2 and anti-CD47 in syngeneic and xenograft mouse models of neuroblastoma, where the combination eradicates tumors, as well as osteosarcoma and small-cell lung cancer, where the combination significantly reduces tumor burden and extends survival. This synergy is driven by two GD2-specific factors that reorient the balance of macrophage activity. Ligation of GD2 on tumor cells (a) causes upregulation of surface calreticulin, a pro-phagocytic 'Eat me' signal that primes cells for removal and (b) interrupts the interaction of GD2 with its newly identified ligand, the inhibitory immunoreceptor Siglec-7. This work credentials the combination of anti-GD2 and anti-CD47 for clinical translation and suggests that CD47 blockade will be most efficacious in combination with monoclonal antibodies that alter additional pro- and anti-phagocytic signals within the tumor microenvironment.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Óseas / Antígeno CD47 Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Nat Med Asunto de la revista: BIOLOGIA MOLECULAR / MEDICINA Año: 2022 Tipo del documento: Article País de afiliación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Óseas / Antígeno CD47 Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Nat Med Asunto de la revista: BIOLOGIA MOLECULAR / MEDICINA Año: 2022 Tipo del documento: Article País de afiliación: Estados Unidos