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Co-Culture Poster 4257 AACR_28Mar2024.pdf (2)

Poster

AACR 2021 Poster

In Vitro and In Vivo Model for Evaluation of Novel Therapeutic Agents in Patient derived-Lymphoblastic Leukemia (B-ALL)

Summary

B-cell Acute Lymphoblastic Leukemia (B-ALL) is a hematological malignancy marked by the transformation and proliferation of B-cell progenitors. While young patients respond well to standard treatments, a subset is chemo-resistant with high relapse rates, and prognosis is worse in adults. This highlights the need for novel, targeted therapies. The lack of suitable in vitro culture conditions for primary B-ALL cells has hindered drug evaluation. We have developed a short-term culture system that supports the survival of primary B-ALL cells for ex vivo screening of therapeutic agents, with cell growth/viability assessed using the CellTiter-Glo assay.

  • Out of 13 primary B-ALL models, 5 proliferated and 5 remained stable and viable until day 3, with all models expressing CD19 and CD20. The models showed varied sensitivity to chemotherapeutic drugs (doxorubicin, vincristine, imatinib, and cytarabine), with BCR-ABL+ models being sensitive to imatinib, and BCR-ABL- models being resistant.

  • A patient-derived xenograft (PDX) preclinical B-ALL model was developed by transplanting B-ALL PBMCs into sub-lethally irradiated NCG mice, achieving 100% engraftment in all models, with latency of engraftment ranging from 15 days to 3.5 months.

  • Flow cytometry analysis of engrafted mice showed 30-95% hCD45+, hCD19+ cells in bone marrow and 40-98% B-ALL cell infiltration in the spleen. Serial transplantation maintained similar engraftment and immunophenotype, establishing a reliable in vitro screening platform and a passable PDX model for in vivo drug efficacy studies.

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