Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Concept Videos

The Tumor Microenvironment02:17

The Tumor Microenvironment

6.5K
Every normal cell or tissue is embedded in a complex local environment called stroma, consisting of different cell types, a basal membrane, and blood vessels. As normal cells mutate and develop into cancer cells, their local environment also changes to allow cancer progression. The tumor microenvironment (TME) consists of a complex cellular matrix of stromal cells and the developing tumor. The cross-talk between cancer cells and surrounding stromal cells is critical to disrupt normal tissue...
6.5K
Tumor Immunotherapy01:27

Tumor Immunotherapy

464
Immunotherapy is a treatment that boosts or manipulates the immune system to fight diseases, including cancer. For instance, by stimulating an immune response through vaccinations against viruses that cause cancers, like hepatitis B virus and human papillomavirus, these diseases can be prevented. Nonetheless, some cancer cells can avoid the immune system due to their rapid mutation and division. The immune response to many cancers involves three phases: elimination, equilibrium, and escape.
464

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

Targeted degradation of hepatic KEAP1 mitigates drug-induced liver injury via dual boosting NRF2 and PGAM5 signaling.

Redox biology·2026
Same author

<i>In vitro</i> screening of active flavonoid components from <i>B. javanica</i> flavonoids against protoscoleces of <i>Echinococcus granulosus</i> from sheep.

Frontiers in veterinary science·2026
Same author

The Effects of Myopia on Optic Disc Morphology and Retinal Vascular Geometry: A Study of Anisometropic Eyes.

Translational vision science & technology·2026
Same author

Application of synthetic patient samples in biochemistry laboratory case-based learning course to improve biosafety.

BMC medical education·2026
Same author

Highly Conductive and Durable MXene/CNC/PEDOT:PSS-PNIPAm Hydrogel for Bioinspired Self-Sensing Soft Actuators.

ACS applied materials & interfaces·2026
Same author

Corrigendum to "CXCR2 antagonism promotes oligodendrocyte precursor cell differentiation and enhances remyelination in a mouse model of multiple sclerosis" [Neurobiology of Disease 2019 Nov 5; 134:104630].

Neurobiology of disease·2026

Related Experiment Video

Updated: May 28, 2025

Generation of Orthotopic Pancreatic Tumors and Ex vivo Characterization of Tumor-Infiltrating T Cell Cytotoxicity
06:16

Generation of Orthotopic Pancreatic Tumors and Ex vivo Characterization of Tumor-Infiltrating T Cell Cytotoxicity

Published on: December 7, 2019

12.6K

Enzyme-Activated Orthogonal Proteolysis Chimeras for Tumor Microenvironment-Responsive Immunomodulation.

Caixia Sun1, Songhan Liu1, Jun Wei Lau2

  • 1School of Chemistry, Chemical Engineering and Biotechnology, Nanyang Technological University, 21 Nanyang Link, Singapore, 637371, Singapore.

Angewandte Chemie (International Ed. in English)
|February 11, 2025
PubMed
Summary

This study introduces novel enzyme-activated clickable PROTACs that degrade cancer-driving proteins specifically within the tumor microenvironment (TME). These PROTACs improve drug delivery and enhance anti-tumor immunity by downregulating PD-L1.

Keywords:
PROTACsbioorthogonal click chemistryimmunomodulationtarget protein degradationtumor microenvironment-responsive

More Related Videos

Tumor Transplantation for Assessing the Dynamics of Tumor-Infiltrating CD8+ T Cells in Mice
07:36

Tumor Transplantation for Assessing the Dynamics of Tumor-Infiltrating CD8+ T Cells in Mice

Published on: June 12, 2021

6.4K
In Vitro Tumor Cell Rechallenge For Predictive Evaluation of Chimeric Antigen Receptor T Cell Antitumor Function
08:04

In Vitro Tumor Cell Rechallenge For Predictive Evaluation of Chimeric Antigen Receptor T Cell Antitumor Function

Published on: February 27, 2019

11.6K

Related Experiment Videos

Last Updated: May 28, 2025

Generation of Orthotopic Pancreatic Tumors and Ex vivo Characterization of Tumor-Infiltrating T Cell Cytotoxicity
06:16

Generation of Orthotopic Pancreatic Tumors and Ex vivo Characterization of Tumor-Infiltrating T Cell Cytotoxicity

Published on: December 7, 2019

12.6K
Tumor Transplantation for Assessing the Dynamics of Tumor-Infiltrating CD8+ T Cells in Mice
07:36

Tumor Transplantation for Assessing the Dynamics of Tumor-Infiltrating CD8+ T Cells in Mice

Published on: June 12, 2021

6.4K
In Vitro Tumor Cell Rechallenge For Predictive Evaluation of Chimeric Antigen Receptor T Cell Antitumor Function
08:04

In Vitro Tumor Cell Rechallenge For Predictive Evaluation of Chimeric Antigen Receptor T Cell Antitumor Function

Published on: February 27, 2019

11.6K

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Cancer Research

Background:

  • Tumor microenvironment (TME) modulation is crucial for effective cancer therapy.
  • Proteolysis-targeting chimeras (PROTACs) offer a promising approach for targeted protein degradation.
  • Current PROTACs face challenges in selectivity, synthesis, and in vivo efficacy due to their complex structures.

Purpose of the Study:

  • To develop a novel TME-responsive, enzyme-activated clickable PROTAC system.
  • To overcome limitations of conventional PROTACs, including selectivity and tumor penetration.
  • To investigate the potential of these PROTACs in cancer therapy and immunomodulation.

Main Methods:

  • Design and synthesis of enzyme-activated clickable PROTACs utilizing a peptide-tagged pomalidomide derivative and a cyanobenzothiazole-labeled epigenetic protein-ligand.
  • Tumor-specific cleavage by cathepsin protease leading to in situ degrader formation.
  • Systematic protein profiling and proteomic analysis to assess target degradation and off-target effects.
  • In vitro and in vivo evaluation of PROTAC efficacy, including tumor penetration and PD-L1 downregulation.

Main Results:

  • The clickable PROTACs demonstrated tumor-specific cleavage and degradation of epigenetic proteins within the TME.
  • Achieved superior tumor penetration compared to conventional high-molecular-weight PROTACs.
  • Efficiently downregulated programmed death-ligand 1 (PD-L1), a key immune checkpoint, both in vitro and in vivo.

Conclusions:

  • Enzyme-activated clickable PROTACs represent a novel strategy for targeted cancer therapy.
  • This approach enhances drug delivery and efficacy by leveraging TME-specific activation.
  • The developed PROTACs show significant potential for remodeling the TME and improving anti-tumoral immunomodulation.