Mosunetuzumab is a T-cell reliant bispecific antibody that binds to CD3 and CD20 to trigger T-cell mediated B-cell death.
However, cytokine release syndrome, which has the potential to limit dose and efficacy, can result from powerful immune stimulation with T-cell focused treatments.
We created a novel mechanistic model of immune and antitumor responses to the T-cell bispecifics (mosunetuzumab and blinatumomab), taking into account the dynamics of B- and T-lymphocytes in circulation, lymphoid tissues, and tumors, in order to better understand the mechanisms underlying safety and efficacy as well as to explore safety mitigation strategies.
Using mosunetuzumab nonclinical and blinatumomab clinical data, the model was created and validated. The initial step-fractionated dose was projected to minimize systemic T-cell activation and cytokine release without impairing tumour response.
Simulations described the mechanisms underlying the observed cell and cytokine (IL6) dynamics. The Phase I clinical study for mosunetuzumab was changed to a step-fractionated treatment schedule as a result of these findings, allowing for the safer administration of greater dosages.
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Embryonic stem cells. These stem cells come from embryos that are three to five days old. At this stage, an embryo is called a blastocyst and has about 150 cells. These are pluripotent (ploo-RIP-uh-tunt) stem cells, meaning they can divide into more stem cells or can become any type of cell in the body.
<span>Vertebrates that are endothermic are birds and mammals. Endothermic organisms are able to regulate their own body temperature while ectothermic organisms depend on the temperature of the environment. Birds and mammals are endothermic organisms. Fish, amphibians, and reptiles are ectothermic organisms.</span>
The light-dependent reactions involving photosystems I and II.
