Models for evaluating cancerous stem cell-targeting therapeutics

Cancer formation and progression are largely driven by cancerous stem cells (CSCs). CSCs are typically not eliminated by conventional treatment approaches, creating an unmet need for developing innovative therapeutics to prevent disease recurrence and relapse. While CSCs are rare in patient specimens, Stelexis Therapeutics, through its proprietary Tumor OriginTM Platform, can isolate and expand this rare CSC population from a wide collection of patient-derived samples, while maintaining their clinical relevance. Utilizing the Tumor OriginTM Platform, we were able to discover novel, druggable CSC targets and to develop high affinity neutralizing monoclonal antibodies (mAbs). Patient-derived models have been instrumental in evaluating our therapeutic mAbs in both AML and solid tumors. In AML, an in vitro drug sensitivity screen guided our selection of models for in vivo PDX studies. Immuno-deficient mice were injected with patient-derived AML cells, monitored for engraftment, and treated with our mAbsas mono therapy or in combination with standard of care. Study readout comprised of monitoring disease burden, as indicated by the count of different human hematopoietic cells in the blood, the bone marrow and the spleen. To study the effect of our therapeutic antibodies on solid tumors, we employed two models: PDX models engrafted in the flank, followed by tumor volume monitoring, and lung inflammation and metastasis assessment, and cancer cells injected into the tail vein and assessed for lung seeding, metastasis formation and tissue inflammation. Key points: •There is a great unmet need in targeting CSCs for treating cancer progression and relapse •Stelexis Therapeutics has developed the Tumor OriginTM Platform for the isolation, expansion and maintenance of patient-derived CSCs that enables novel target & drug discovery •Patient-derived models have supported our pre-clinical proof of concept studies in AML & solid tumors, both in vitro & in mouse xenograft models