Humanized Lag-3 Animal Models for Anti-Tumor Immunity Assessment
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Solution Overview
Problem
Current systems lack effective methods to develop and assess therapeutics that activate anti-tumor immunity and understand the mechanisms by which cancer cells inhibit immune responses, particularly in T cells, hindering the identification of promising cancer treatments.
Innovation Solution
Engineering non-human animals with humanized Lymphocyte-activation gene 3 (Lag-3) and Programmed cell death 1 (PD-1) genes to create in vivo models for testing cancer therapeutics, utilizing genetic material from both human and non-human species to express functional Lag-3 polypeptides that promote anti-tumor immunity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If non-human animals are engineered with humanized Lag-3 and PD-1 genes to create in vivo models for testing cancer therapeutics, then the ability to assess therapeutic efficacy and immune response modulation is improved, but the device complexity and manufacturing difficulty increase
Solution Approach 1:
The patent uses non-human animals as intermediary models that express humanized Lag-3 and PD-1 proteins, allowing human therapeutic responses to be studied in vivo without directly using human subjects. This intermediary system bridges the gap between in vitro studies and human clinical trials, enabling reliable therapeutic efficacy assessment while avoiding the complexities of direct human experimentation.
2Adaptability or versatility
If genetic material from both human and non-human species is combined to express functional Lag-3 polypeptides, then the ability to mimic human immune responses is improved, but the manufacturing precision and genetic engineering difficulty increase
Solution Approach 1:
The patent applies local quality by introducing only specific human gene sequences (Lag-3 and PD-1) into the non-human animal genome rather than attempting to humanize the entire organism. This targeted approach allows the animals to express humanized immune checkpoint proteins with high precision while maintaining the simplicity of non-human animal genetics for other physiological functions.
Data Source
AI summary
Non-human animals, and methods and compositions for making and using the same, are provided, wherein the non-human animals comprise a humanization of a Lymphocyte activation gene 3 (Lag3). The non-human animals may be described, in some embodiments, as having a genetic modification to an endogenous Lag3 locus so that the non-human animals express a Lag3 polypeptide that includes a human portion and an endogenous portion (e.g., a non-human portion).