cellPrism® is a drug development platform offering customizable cell-based in vitro assays using optimally sourced and processed primary cells (blood and bone marrow cells) from multiple species. By using primary cells in our assays cellPrism is able to provide clients with the best clinically relevant data, including high content readouts for numerous blood diseases and disorders. CellPrism’s predictive assays can be applied to a variety of program challenges including neutropenia, thrombocytopenia, and immuno-oncology.
Abnormally low numbers of platelets in the blood. Platelets are derived from megakaryocytes and helps stop bleeding by clumping and clotting blood vessel injuries. Therefore, if a drug treatment inadvertently targets the megakaryocytes, there will be a decreased production of platelets. Alternatively, a drug may inadvertently cause an increased destruction of the mature platelets, both scenarios will result in thrombocytopenia.
2. Severe Anemia
Abnormally low numbers of red blood cells which may be the result of blood loss, an inability to produce adequate red blood cells or a breakdown of the red blood cell. Blood loss may result from injury, whereas the inability to produce red blood cells may be due to deficiencies in iron or vitamin B12. Another potential reason for a decrease in red blood cells may be side effects of certain drug treatments.
Abnormally low numbers of neutrophils (a type of white blood cell) in the blood. The neutrophils make up between 60% -70% of the circulating white blood cells and serve as the primary defense against infections by destroying bacteria, bacterial fragments, and viruses in the blood. Neutropenia is often a side effect of drug treatments and this effect may be acute or chronic and can become a rate limiting factor for continued treatment. Since neutrophils have very short half-lives, any drugs that inadvertently affect them can cause serious medical complications.
Certain therapies, often (but not always) targeting NHL (Non-Hodgkin Lymphoma) related diseases, cause off target cell death of lymphocytes (T cells, B cells and NK cells). The toxicity can be species dependent. For example, some drugs can cause severe lymphopenia in small animal models but have little toxicity on human cells. This issue can make preclinical development challenging and frustrating.
1. Antibody Testing
Antibody-Drug Conjugates are being engineered with more stable toxic payloads, recombinant antibodies are being engineered to have higher target and Fc receptor affinity, bispecific antibodies are being created that redirect T cells to diseased cells, and immune checkpoint modulators are being developed to enhance a patient’s own immune response to cancer.
2. Cytokine Storm
A cytokine storm is a potentially lethal adverse effect of some immunomodulatory therapies. It is caused when a pro-inflammatory cytokine feedback loop is created by a treatment. Since the TGN-1412 clinical trial disaster, regulatory bodies have been more diligent about requiring certain classes of novel therapeutics to be assessed for their potential to trigger a cytokine storm.
Immune monitoring is an important part of many preclinical and clinical programs. T, B and NK cells can be enumerated along with more recently discovered cells such as myeloid derived suppressor cells and dendritic cells. In diseased patients, the presence of important markers can be monitored over the course of a clinical trial to assess if the treatment is influencing the diseased cells.
The success of anti-PD1 therapy has generated enormous interest in creating novel therapies to enhance the immune system’s inherent ability to identify and kill cancer cells. The targets of immuno-oncology therapy can include immune checkpoints, such as PD-1 and CTLA-4, as well as markers associated with T cell exhaustion such as Tim-3, Lag-3 and TIGIT.
5. Target Validation
Target validation is the process by which newly discovered cellular pathways that are believed to play a role in diseases are confirmed. An important part of target validation is confirming that the therapeutic target is both present in the primary diseased cells, and that disruption of the target elicits a desired effect (e.g. induction of apoptosis).
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Tags: antibody testing, assay development, Atlantis Bioscience, cell bank development, CRO, cytokine storm risk analysis, drug development, drug discovery, Flow cytometry, immuno-oncology, lymphophenia, neutropenia, Preclinical Oncology, predictive and investigative toxicology, primary cells, ReachBio, severe anemia, thrombocytopenia