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Poster

SITC 2025 Poster #316

A Humanized In Vivo Platform for Modeling Primary Acute Myeloid Leukemia to Advance Immunotherapy, Bispecific, and CAR-T Cell Development

Summary

Immunotherapies in AML demand models that retain human immune function and patient tumor complexity. Champions, with Taconic, developed a humanized AML platform using NOG-EXL mice that first receive CD34+ HSCs to establish multilineage human immunity, then are co-engrafted with primary, never-passaged AML PDX samples selected from our AML bank. Longitudinal flow cytometry tracks immune compartments and leukemic populations in both bone marrow and peripheral blood, giving a clear view of disease kinetics and tumor-immune interplay. This system supports evaluation of monoclonals, bispecifics, CAR-T, and combinations in a clinically relevant setting.

CD34+ HSC-engrafted NOG-EXL mice showed robust myeloid and lymphoid reconstitution. Subsequent AML PDX engraftment produced consistent progression within an immune-engaged microenvironment. A custom multiparametric flow panel identified human immune subsets alongside AML blasts, progenitors, and monoblasts, enabling functional assessment of tumor-immune interactions and therapy response in vivo.

Learning outcomes:

  • Understand how dual engraftment in NOG-EXL, first CD34+ HSCs then primary AML, preserves human immune functionality while maintaining native AML heterogeneity.

  • See how longitudinal flow cytometry in bone marrow and peripheral blood quantifies both AML burden and human immune subsets, including T cells, B cells, NK cells, macrophages, and M2 macrophages.

  • Recognize how the model captures an immunosuppressive marrow context, aligning with patient biology and supporting realistic immunotherapy readouts.

  • Learn how this platform enables head-to-head testing of immune-based therapies and combinations, with readouts that inform mechanism, dosing strategy, and go or no go decisions.

  • Identify next steps, such as correlating immune kinetics with efficacy markers and expanding to HLA-aware donor selection to refine translational relevance.

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