Hematotoxicity and Selectivity Assays
Hematotoxicy is a major toxicity concern of oncology drug candidates, for both hematological and solid tumors. Hematopoietic Stem Cells (HSCs) are the responsible to replenish mature blood cells after hematopoietic stresses. One of the most common dose limiting adverse effects in cancer treatment is myelosuppression.
- Vivia Biotech provides a Native Environment assays to measure depletion of different subsets of CD34+ progenitors in Normal Bone Marrow (NBM) or hematological diseases, to potentially screen drug candidates and combinations for hematotoxicity, as well as personalize therapy to the individual sensitive patient at risk.
We can measure whether your compounds kill selectively
We test the hypothesis your compounds are selective, but it does not imply toxicity
Tumor vs Progenitor Cells in AML BM Samples: Eliminate immature progenitors responsible for relapse
Ex vivo Therapeutics Index: Tumor vs Progenitor Cells
Extreme resistance myeloid progenitors
Suggest no hematotoxicity, very selective
plasma cells Ideal patient
Suggest no hematotoxicity, very selective
plasma cells Ideal patient
More sensitive for myeloid progenitors
than for plasma cells High hematotoxicity
Unfit patient
than for plasma cells High hematotoxicity
Unfit patient
- Bortezomib dose response curves in MM BM patient samples
Daratumumab is less active on Healthy CD34+CD38- progenitor cells
Dose response curves of daratumumab in plasmatic and progenitor cells
Daratumumab Specificity & Therapeutic Window Ex Vivo is Higher at High CD38 Expression
Correlation between CD38 expression on different cellular subsets and activity (AUC)
in MM patients. Daratumumab is Less Active on T, NK, or Progenitor Cells
in MM patients. Daratumumab is Less Active on T, NK, or Progenitor Cells
Highlights
- Hematotoxicity Assay for your drug: we can analyze depletion of hematopoietic progenitors in Normal BM
- We measure whether your compounds kill selectively: leukemic vs healthy lymphocytes
- Myelosupression assay may indicate drug hematotoxicity among analogue compounds
- We evaluate drug activity on progenitor cells simultaneously with the tumor cell subpopulation.
- Ex vivo therapeutic index: Your drug can selectively impact on how your compound is good for transplant conditioning or is bad for induction.
- Specificity and therapeutic window for NK Engagers like Daratumumab
- Specificity & Therapeutic Window ex vivo of daratumumab depends on CD38 expression in tumoral cells.
- Hematotoxicity of novel and targeted drugs on myeloid precursors. Check if synergistic combinations for tumor cells are not more synergistic for myelosuppression: Prevent highly hematotoxic combinations
- Vivia NE Hematotoxicity Assays can be applied early in discovery to select among hit candidates, or in development to identify combinations with synergistic hematotoxicity
- Vivia NE Hematotoxicity Assays are good to select drug candidates in hematological diseases and also in solid tumors.