Immune Cells with Reduced Androgen Receptor for Prostate Cancer Therapy
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Solution Overview
Problem
Current immunotherapy treatments for advanced prostate cancer, particularly in castration-resistant prostate cancer, are ineffective due to the suppressive effect of androgens on the immune system, which hinder the function of immune cells such as T cells, regulatory T cells, macrophages, dendritic cells, natural killer cells, and B cells, limiting their anti-tumor potential.
Innovation Solution
Reducing androgen receptor (AR) activity in immune cells through genetic repression or pharmacologic inhibition enhances the function of these cells, allowing for improved anti-tumor responses by modifying leukocytes to decrease AR expression or activity, thereby enhancing cell therapies like CAR-T cell therapy, adoptive cell therapy, and dendritic cell therapy.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Strength
If androgen deprivation therapy is administered to inhibit tumor cell growth, then cancer cell growth is suppressed, but immune cell function is further suppressed
Solution Approach 1:
The patent applies local quality by differentiating the treatment approach for different cell types. Immune cells receive AR inhibition to enhance their function, while tumor cells are treated with androgen deprivation therapy to suppress growth. This selective differential treatment resolves the contradiction by allowing AR inhibition benefits for immune cells without compromising tumor cell suppression.
Solution Approach 2:
The patent introduces an intermediary approach by using cell therapy products with reduced AR expression as a mediator. These modified immune cells serve as intermediaries that can function effectively in the androgen-deprived environment, bridging the gap between androgen deprivation therapy and immune cell function requirements.
2Reliability
If checkpoint blockade immunotherapy is used to treat prostate cancer, then immune response is enhanced, but effectiveness is reduced in castration-resistant prostate cancer
Solution Approach 1:
The patent applies preliminary action by pre-modifying immune cells to have reduced AR expression before administering checkpoint blockade therapy. This preparatory modification ensures that immune cells are primed and capable of effective function even in the androgen-rich environment of castration-resistant prostate cancer, resolving the contradiction between maintaining immune response and achieving anti-tumor efficacy.
3Adaptability or versatility
If androgen levels are maintained in the body, then normal physiological functions are preserved, but immune cell anti-tumor potential is suppressed
Solution Approach 1:
The patent applies local quality by selectively reducing AR expression only in immune cells while maintaining normal androgen levels in the body. This localized modification allows physiological functions to remain intact while specifically enhancing anti-tumor potential of immune cells, resolving the contradiction between maintaining adaptability and improving productivity.
Data Source
AI summary
The present disclosure relates generally to dis-arming immune cell product sensitivity to androgens. Provided herein are methods, systems, and compositions for disarming androgen receptor (AR) activity in immune cells, for instance in the context of CAR-T cell therapy, allogenic T cell therapy, DC vaccines, macrophage therapy, myeloid/macrophage antigen receptor therapy, NK cell therapy, and so forth. Different methods for reducing AR function are described.