Looking for breakthrough ideas for innovation challenges? Try Patsnap Eureka!

Tumor immunotherapy

An engineering, circuit technology with applications in the fields of synthetic biology and immunology to address the problems of incurable metastatic disease, morbidity and toxicity

Inactive Publication Date: 2018-07-31
MASSACHUSETTS INST OF TECH
View PDF5 Cites 1 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] Existing treatments for many cancers (e.g., ovarian cancer), such as chemotherapy and targeted therapy, do not cure metastatic disease and prevent tumor recurrence
In addition, standard-of-care treatments such as chemotherapy can cause significant morbidity and toxicity

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
  • Tumor immunotherapy
  • Tumor immunotherapy
  • Tumor immunotherapy

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0170] Two human promoters were used as promoter inputs for the engineered genetic circuits used in this example. These human promoters SSX1 (input 1) and H2A1 (input 2) are overexpressed in many human cancers (input 1 encodes mKate2 output containing intervening mirFF4) ( Figure 4A ). Measurement of different circuit configurations relative to (a) the number of perfectly matched mirFF4 binding sites (FF4-BS) encoded in input 1 (downstream of mK2) and (b) two different configurations of the 'sponge' construct in input 2 mKate2 output level. Figure 4B , x-axis annotation: M# represents the number of mirFF4 binding sites (FF4-BS) encoded downstream of mKate2 / mirFF4 that input 1 has. For example, M3 represents input 1 with 3 perfectly matching mirFF4 binding sites (FF4-BS) ( Figure 4A ). S0, S1 and S2 represent three different sponge / input 2 configurations. S0 is a negative control transcript that does not have a mirFF4 binding site. S1 is a decoy transcript (Decoy trans...

Embodiment 2

[0173] The engineered genetic circuit (G5) described in this example is based on the mKate2-encoding circuit (AND gate) described in Example 1, with the difference that the product of the AND gate is not mKate2 but a synthetic transcription factor (in Figure 6A are noted as "TF"). Although TF can be any transcriptional activator, such as rtTA3, TALE-TF, and ZF-TF, in this example, TF is the fusion protein GAL4BD-VP16AD (yeast GAL4 DNA-binding domain fused to viral VP16 transcriptional activation domain ). Alternatively, this could also be a transcriptional repressor, eg GAL4BD-KRAB. Because the export is a transcription factor rather than a reporter / effector protein, it can regulate the expression of multiple exports encoded downstream of the TF target promoter. In this example, the target promoter (annotated as P3) was a synthetic G5 promoter consisting of a minimal viral or human promoter with 5 upstream GAL4 DNA binding sites. The I / O profile of the synthetic promoter c...

Embodiment 3

[0175] Example 3. BiTEs and STEs Trigger Robust Tumor Killing

[0176] HEK-293T cells

[0177] Anti-HER2 bispecific T cell engager (BiTE) and surface T cell engager (STE) trigger T cells to mediate robust tumor killing and IFN-γ secretion ( Figure 8 ). HEK-293T (minimally expressing HER2) cells were transfected with various DNA constructs as indicated. 48 hours after transfection, various HEK-293T cells were harvested and co-cultured with human T cells for 5 hours or 24 hours. The 5-hour cytotoxicity of T cells was measured by lactate dehydrogenase (LDH) release assay (Korzeniewski C and Callewaert DM, Journal of Immunological Methods, 1983, 64(3):313-320, incorporated herein by reference ), and 24-h IFN-γ secretion by T cells was measured by IFN-γ ELISA. The data indicate that T cells mediate robust tumor killing and IFN-γ secretion against BiTE-secreting tumor cells (Groups 1-2). Tumor killing and IFN-γ secretion correlated with HER2 expression levels on tumor cells (G...

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

No PUM Login to View More

Abstract

Aspects of the present disclosure provide a platform that triggers potent and effective immunotherapy against tumors from within tumors themselves, thus overcoming limitations of existing cancer immunotherapies and tumor-detecting gene circuits.

Description

[0001] related application [0002] This application claims the benefit under 35 U.S.C. §119(e) of U.S. Provisional Application No. 62 / 181,906, filed June 19, 2015, and U.S. Provisional Application No. 62 / 325,314, filed April 20, 2016, each of which is incorporated by reference in its entirety Incorporated into this article. technical field [0003] Some aspects of the present disclosure relate to the general field of biotechnology, and more specifically to the fields of synthetic biology and immunology. Background technique [0004] Existing treatments for many cancers (eg, ovarian cancer), such as chemotherapy and targeted therapy, fail to cure metastatic disease and prevent tumor recurrence. Furthermore, standard-of-care treatments such as chemotherapy can cause significant morbidity and toxicity. New therapeutic strategies are needed to treat primary and metastatic ovarian cancer and achieve long-term efficacy. Contents of the invention [0005] In some aspects, pro...

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
no application Login to View More
Patent Type & Authority Applications(China)
IPC IPC(8): C12N15/00C12N15/10C12N15/11C12N15/63C12N15/113C12Q1/6886A61K39/395
CPCG01N33/6845A61P35/00A61P43/00C07K14/4702C07K16/2809C07K16/32C07K2317/622C07K2319/03C12N15/85C12N2830/002
Inventor 蒂莫西·冠-塔·卢利奥尔·尼西姆吴名儒
Owner MASSACHUSETTS INST OF TECH
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Patsnap Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Patsnap Eureka Blog
Learn More
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic, Popular Technical Reports.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com