Childhood Cancer Data Initiative Annual Symposium (Abstract Registration): Submission #40

serial: '40'
sid: '148323'
uuid: beae2b78-e81e-4bc7-ab77-d84f8942320c
uri: /nci/ccdisymposium/abstract
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completed: '1754578067'
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langcode: en
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data:
  authors_:
    - add_author_degree: ''
      add_author_first_name: Ying
      add_author_last_name: Wang
      add_author_middle: ''
      add_author_organization: 'Baylor College of Medicine'
    - add_author_degree: 'M.D. Ph.D.'
      add_author_first_name: Linjie
      add_author_last_name: Guo
      add_author_middle: ''
      add_author_organization: 'Baylor College of Medicine'
    - add_author_degree: ''
      add_author_first_name: Akshaya
      add_author_last_name: Adaikkalavan
      add_author_middle: ''
      add_author_organization: 'Baylor College of Medicine'
    - add_author_degree: Ph.D.
      add_author_first_name: Amy
      add_author_last_name: Courtney
      add_author_middle: N.
      add_author_organization: 'Baylor College of Medicine'
    - add_author_degree: 'M.D. Ph.D.'
      add_author_first_name: Xavier
      add_author_last_name: Rios
      add_author_middle: ''
      add_author_organization: 'Baylor College of Medicine'
    - add_author_degree: Ph.D.
      add_author_first_name: Xin
      add_author_last_name: Xu
      add_author_middle: ''
      add_author_organization: 'Baylor College of Medicine'
    - add_author_degree: ''
      add_author_first_name: Michael
      add_author_last_name: Wood
      add_author_middle: S.
      add_author_organization: 'Baylor College of Medicine'
    - add_author_degree: Ph.D.
      add_author_first_name: Erica
      add_author_last_name: Pierro
      add_author_middle: Di
      add_author_organization: 'Baylor College of Medicine'
    - add_author_degree: Ph.D.
      add_author_first_name: Xin
      add_author_last_name: Zhou
      add_author_middle: ''
      add_author_organization: 'University of North Carolina at Chapel Hill'
    - add_author_degree: M.D.
      add_author_first_name: Gianpietro
      add_author_last_name: Dotti
      add_author_middle: ''
      add_author_organization: 'University of North Carolina at Chapel Hill'
    - add_author_degree: 'M.D. Ph.D.'
      add_author_first_name: Leonid
      add_author_last_name: Metelitsa
      add_author_middle: S.
      add_author_organization: 'Baylor College of Medicine'
  abstract: |
    Adoptive cell therapies, including T and natural killer T (NKT) cells expressing GD2 specific chimeric antigen receptors (CAR), have shown promise in treating relapsed/refractory (r/r) neuroblastoma (NB) but remain non-curative. A significant barrier to improving these therapies is the reliance on xenogeneic models, which fail to capture the full spectrum of innate and adaptive immune responses. We recently reported that CAR NKTs have superior in vivo antitumor activity in several syngeneic tumor models (PMID: 39354225), but not in NB due to the lack of relevant models.

    To develop syngeneic NB models for evaluating CAR T and CAR NKT cell therapies, murine NB cell lines expressing GD2 and B7H3 were created via lentiviral transduction and optimized through orthotopic implantation into C57BL/6 mice. These cell lines were engineered for cyclophosphamide (Cy) resistance to model r/r NB and support lymphodepleting preconditioning. The tumor microenvironment (TME) was characterized using flow cytometry. Murine T and NKT cells were transduced with GD2/B7H3 CARs encoding CD28 or 41BB costimulatory domains. 

    Results showed that GD2 and B7H3 NB models exhibited high tumor inoculation rates and stable antigen expression. The TME featured diverse immune populations. In vitro, CAR T/NKTs eliminated antigen-specific NB cells. In vivo, both therapies reduced tumor burden post Cy preconditioning, mirroring clinical trial outcomes but without achieving complete tumor control.

    To conclude, we developed Cy resistant syngeneic orthotopic NB models with stable GD2 and B7H3 expression. These models enable a detailed study of cell therapies in the context of an intact immune system and TME.
  abstract_title_: 'Optimized Syngeneic Neuroblastoma Models to Advance Cell Therapies '
  email_address_: ying.wang3@bcm.edu
  institution_: 'Baylor College of Medicine'
  presenting_author_: 'Ying Wang'