OsteoBites Welcomes Sabina Kaczanowska, PhD

Thu Aug 01 2024 at 03:00 pm to 04:00 pm UTC-04:00

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MIB Agents
Publisher/HostMIB Agents
OsteoBites Welcomes Sabina Kaczanowska, PhD
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Immune determinants of CAR-T cell expansion in solid tumor patients receiving GD2 CAR-T cell therapy
About this Event

Sabina Kaczanowska’s research focus is to understand the role of the immune system in shaping the microenvironment of metastasis during cancer progression. Specifically, she is investigating how myeloid cells orchestrate the immunosuppressive program in the pre-metastatic niche and how we can apply this knowledge of myeloid biology to design new immunotherapeutic strategies for the treatment of solid tumors. She will join us on OsteoBites to discuss her recently published paper on Immune determinants of CAR-T cell expansion in solid tumor patients receiving GD2 CAR-T cell therapy.

Chimeric antigen receptor T cells (CAR-Ts) have remarkable efficacy in liquid tumors, but limited responses in solid tumors. The NCI conducted a Phase I trial (NCT02107963) of GD2 CAR-Ts (GD2-CAR.OX40.28.z.iC9), demonstrating feasibility and safety of administration in children and young adults with osteosarcoma and neuroblastoma. Since CAR-T efficacy requires adequate CAR-T expansion, patients were grouped into good or poor expanders across dose levels. Patient samples were evaluated by multi-dimensional proteomic, transcriptomic, and epigenetic analyses. T cell assessments identified naive T cells in pre-treatment apheresis associated with good expansion, and exhausted T cells in CAR-T products with poor expansion. Myeloid cell assessment identified CXCR3+ monocytes in pre-treatment apheresis associated with good expansion. Longitudinal analysis of post-treatment samples identified increased CXCR3- classical monocytes in all groups as CAR-T numbers waned. Together, our data uncover mediators of CAR-T biology and correlates of expansion that could be utilized to advance immunotherapies for solid tumor patients.

After a short presentation on this research, she will take questions from attendees. Share your questions in advance with us at [email protected].

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