DARICs for Controlled CD33 Targeting in T Cell Therapy
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Solution Overview
Problem
Current adoptive cell therapies, such as CAR T cell therapy, lack spatial and temporal control over cellular signal initiation and downstream responses, leading to potential side effects like cytokine release syndrome.
Innovation Solution
The development of dimerizing agent regulated immunoreceptor complexes (DARICs) that recognize CD33, comprising specific polypeptides and bridging factors, to modulate the activity of immune effector cells in a controlled manner.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If adoptive cell therapy is used to treat cancer, then therapeutic efficacy is improved, but spatial and temporal control of cellular signal initiation is lost, leading to harmful side effects
Solution Approach 1:
The patent applies dynamics by making the immunoreceptor complex switchable between inactive and active states through dimerizing agent binding. The complex transitions from a separated inactive state to a bound active state, enabling dynamic control of immune cell activation to achieve therapeutic efficacy while preventing harmful side effects through temporal and spatial regulation.
Solution Approach 2:
The patent uses a dimerizing agent as an intermediary substance that mediates between the immunoreceptor complex components. This intermediary binds to both the first and second immunoreceptor complexes, facilitating their association and activation only when needed, thus providing controlled signal initiation that improves therapeutic outcome while reducing harm.
2Productivity
If adoptive cell therapy is used to treat cancer, then cancer treatment efficacy is enhanced, but temporal control of cellular signal initiation is lost
Solution Approach 1:
The patent implements temporal control through dynamic switching of the immunoreceptor complex between inactive and active states. The complex remains inactive until a dimerizing agent is introduced, at which point it transitions to an active state, enabling precise temporal control of cancer treatment efficacy.
Solution Approach 2:
The patent applies preliminary action by pre-assembling the immunoreceptor complex components in an inactive state before treatment. The complex is prepared in advance but remains dormant until activated by dimerizing agent binding, allowing temporal control over when the therapeutic action begins.
3Reliability
If adoptive cell therapy is used to treat cancer, then therapeutic response is improved, but spatial control of cellular signal initiation is lost
Solution Approach 1:
The patent achieves spatial control by making the immunoreceptor complex dynamically assemble only at locations where dimerizing agent is present. The complex transitions from a dispersed inactive state to a localized active state, enabling spatial control of therapeutic response to improve reliability while minimizing off-target effects.
Solution Approach 2:
The dimerizing agent serves as a spatial mediator that directs the assembly of the immunoreceptor complex to specific locations. By binding to both immunoreceptor components, the dimerizing agent facilitates localized complex formation only where needed, providing spatial control over signal initiation and improving therapeutic response reliability.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
DARICs provide spatial and temporal control over immune effector cell signaling, reducing the risk of side effects and enhancing the efficacy of cancer treatment by targeting CD33-expressing cancer cells.
Implementation Method 1
a bridging factor promotes the formation of a polypeptide complex on the non-natural cell surface with the bridging factor associated with and disposed between the multimerization domains of the first and second polypeptides
Data Source
AI summary
The present disclosure provides improved compositions for adoptive T cell therapies targeting CD33 for treating, preventing, or ameliorating at least one symptom of a cancer, infectious disease, autoimmune disease, inflammatory disease, and immunodeficiency, or condition associated therewith. The present disclosure also relates to adoptive T cell therapies targeting CD33 and another target antigen for treating, preventing, or ameliorating at least one symptom of a cancer, infectious disease, autoimmune disease, inflammatory disease, and immunodeficiency, or condition associated therewith.