Unlock instant, AI-driven research and patent intelligence for your innovation.
Gene-regulating compositions and methods for improved immunotherapy
What is Al technical title?
Al technical title is built by PatSnap Al team. It summarizes the technical point description of the patent document.
A gene regulation and target gene technology, applied in biochemical equipment and methods, chemical equipment and methods, translation products of oncogenes, etc.
Pending Publication Date: 2020-12-04
KSQ THERAPEUTICS INC
View PDF75 Cites 5 Cited by
Summary
Abstract
Description
Claims
Application Information
AI Technical Summary
This helps you quickly interpret patents by identifying the three key elements:
Problems solved by technology
Method used
Benefits of technology
Problems solved by technology
Therefore, there is still much room for improvement in adoptive T-cell therapy, as success has been largely limited to CAR-T cell approaches targeting hematologic malignancies of the B-cell lineage
Method used
the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more
Image
Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
Click on the blue label to locate the original text in one second.
Reading with bidirectional positioning of images and text.
Smart Image
Examples
Experimental program
Comparison scheme
Effect test
Embodiment 1
[0519] Example 1: Materials and methods
[0520] The experiments described here utilize the CRISPR / Cas9 system to modulate the expression of one or more endogenous target genes in different T cell populations.
[0521] I. Materials
[0522] gRNA: All experiments used single-molecule gRNA (sgRNA) unless otherwise stated. Double gRNA molecules were used as indicated and prepared by mixing 200 μM tracrRNA (IDT cat. no. 1072534) with 200 μM target specificity in nuclease-free duplex buffer (IDT cat. crRNA(IDT) was double-stranded for 5 min to form 100 μM tracrRNA:crRNA duplexes, where tracrRNA and crRNA were present in a 1:1 ratio. The targeting sequences of the gRNAs used in the following experiments are provided in Table 10 below.
[0525] Cas9 : Express Cas9 in target cells by introducing Cas9 mRNA or Cas9 protein. Unless otherwise stated, the mRNA encoding Cas9 comprising the nuclear local...
Embodiment 2
[0545] Example 2: Characterization of Edited Receptor Engineered T Cells
[0546] Experiments were performed to purify edited receptor-expressing cells based on CD3 cell surface expression. Prior to engineering, CD8+ T cells express the CD3 molecule on the cell surface as part of a complex containing the TCRα / β chain ( Figure 4A ). T cells were transduced with lentivirus expressing CAR, a guide RNA targeting the TRAC gene, and a guide RNA targeting the B2M gene, which were used to assess editing of non-TCR genes as a surrogate for on-target gene editing. Following lentiviral transduction and Cas9 mRNA electroporation, successfully transduced and edited T cells exhibited loss of surface CD3 expression due to editing of the TRAC gene, and loss of HLA-ABC expression due to editing of the B2M gene ( Figure 4B ). CD3-expressing cells were isolated from a large population using the EasySep Human CD3 Positive Selection Kit (StemCell Tech Cat. No. 18051) ( Figure 4B ). Ce...
Embodiment 3
[0550] Example 3: Via OT1 / B16-O VA CRISPR / C AS 9 Functional genomic screens identify targets for adoptive T cell transfer therapy
[0551] Experiments were performed to identify targets that modulate T cell accumulation in tumors. Pooled CRISPR screens were performed in which each sgRNA pool targeting a single gene was introduced into a population of tumor-specific T cells such that each cell in the population contained a single sgRNA targeting a single gene. To determine the effect of specific genes on T cell accumulation in tumor samples, the frequency of each sgRNA in the T cell population was determined at the beginning of the experiment and compared to the frequency of the same sgRNA at a later time point in the experiment. The frequency of sgRNAs targeting genes that positively regulate T cell accumulation in tumor samples (e.g., genes that positively regulate T cell proliferation, viability, and / or tumor infiltration) are expected to increase over time, while those t...
the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More
PUM
Login to View More
Abstract
The present disclosure provides methods and compositions related to the modification of immune effector cells to increase therapeutic efficacy. In some embodiments, immune effector cells modified to reduce expression of one or more endogenous target genes, or to reduce one or more functions of an endogenous protein to enhance effector functions of the immune cells are provided. In some embodiments, immune effector cells further modified by introduction of transgenes conferring antigen specificity, such as exogenous T cell receptors (TCRs) or chimeric antigen receptors (CARs) are provided. Methods of treating a cell proliferative disorder, such as a cancer, using the modified immune effector cells described herein are also provided.
Description
[0001] Cross References to Related Applications [0002] This application claims U.S. Provisional Application No. 62 / 643,578, filed March 15, 2018; U.S. Provisional Application No. 62 / 692,010, filed June 29, 2018; U.S. Provisional Application No. 62 / 768,428, filed November 16, 2018 ; U.S. Provisional Application No. 62 / 643,587, filed March 15, 2018; U.S. Provisional Application No. 62 / 692,019, filed June 29, 2018; U.S. Provisional Application No. 62 / 768,443, filed November 16, 2018; 2019 U.S. Provisional Application No. 62 / 804,265, filed February 12, 2018; U.S. Provisional Application No. 62 / 643,597, filed March 15, 2018; U.S. Provisional Application No. 62 / 692,100, filed June 29, 2019; U.S. Provisional Application No. 62 / 768,448, filed March 16; U.S. Provisional Application No. 62 / 643,598, filed March 15, 2018; U.S. Provisional Application No. 62 / 692,110, filed June 29, 2018; and November 2018 Priority to U.S. Provisional Application No. 62 / 768,458 filed on the 16th, each of w...
Claims
the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More
Application Information
Patent Timeline
Application Date:The date an application was filed.
Publication Date:The date a patent or application was officially published.
First Publication Date:The earliest publication date of a patent with the same application number.
Issue Date:Publication date of the patent grant document.
PCT Entry Date:The Entry date of PCT National Phase.
Estimated Expiry Date:The statutory expiry date of a patent right according to the Patent Law, and it is the longest term of protection that the patent right can achieve without the termination of the patent right due to other reasons(Term extension factor has been taken into account ).
Invalid Date:Actual expiry date is based on effective date or publication date of legal transaction data of invalid patent.
Login to View More 
Login to View More