Therapeutic Strategies for Targeting Exosomes in TME
Relying on the technology platform of the tumor microenvironment center, Alfa Oncology offers a full range of solutions and services or strategies for investigating therapeutic strategies that for target exosomes in the tumor microenvironment (TME), helping researchers successfully achieve their research goals.
Exosomes are an important component of TME. They act as effective signaling molecules between cancer cells and the surrounding cells that make up TME. Exosomes represent a novel intercellular communication pathway by delivering cargoes such as proteins and nucleic acids to recipient cells. Importantly, it has been well demonstrated that exosome-mediated delivery of such cargo is involved in many pathological processes, such as tumor progression, proliferation, apoptosis, migration, and development of drug resistance. Therefore, exosomes have been used as delivery vehicles for a variety of targeted therapeutic therapies. Compared to artificial nanoscale drug carriers, exosomes are inherently biocompatible and have desirable structural properties, providing a clear advantage for drug delivery.
Fig. 1 Signal transduction pathway of exosomes in tumor microenvironment. (Dai J, et al, 2020)
The most important cells in tumor microenvironment mainly include CAFs, CSCs, MSCs, TMICs, etc. These four types of cells use exosomes to promote EMT, tumor metastasis and drug resistance through a variety of mechanisms. CAFs cancer-associated fibroblasts, CSCs cancer stem cells, MSCs mesenchymal stromal cells, TMICs tumor microenvironmental immune cells.
However, the application of natural targeting exosomes is still problematic in the following aspects: (1) whether unmodified exosomes can accumulate in tumor tissues solely on the basis of natural targeting remains controversial; (2) the safety and efficacy of stem cell-derived exosomes for therapeutic use need to be further investigated; (3) the homing effect of exosomes alone for tumor treatment is likely to cause off-target phenomenon, because the homing effect of stem cells The homing effect of stem cells may not only target tumor tissues, but also migrate to damaged tissues.
To better explore the role of exosomes in tumor targeting research, Alfa Oncology has established an innovative Tumor Microenvironment Center technology platform and is developing several technologies designed to help global collaborators conduct research on exosome targeting of tumors using the tumor microenvironment (TME), which will hopefully provide new ideas on the selection of exosomes as drug delivery vehicles.
Natural targeting provides a basis for exosome-targeted drug delivery. However, this targeting can only be derived from stem cells or tumor cells corresponding to the target cancer, and the source is limited and stability needs to be improved. These factors are important reasons for the off-target phenomenon during drug delivery using natural targeting, making the use of natural targeting of exosomes for drug delivery somewhat limited.
Alfa Oncology is currently focused on the use of the tumor microenvironment (TME) to target exosomes for the treatment of tumors, with the main therapeutic strategy being the artificial modification of exosomes. By combining exosomes with various active molecules that target tumors through chemical, biological and physical means, the drugs can be delivered more precisely to tumor cells or tissues.
- Folate modification
Folic acid receptors are overexpressed on the surface of many tumor cells, and based on this, folic acid is often used to modify exosomes in a targeted manner.
- Antibody modification
Tumor cells express new antigens, called tumor specific antigen (TSA), that are not present on the surface of normal cells. At the same time, tumor cells also overexpress antigens on the surface of normal cells, i.e., tumor associated antigen (TAA). TSA or TAA becomes a breakthrough in targeted therapy for tumors.
- Peptide or aptamer modification
In addition to targeting TSA and TAA with antibodies, there are peptides or proteins that can be used as aptamers to react with ligands on the surface of tumors, thus providing targeting ability for exosomes. Peptides are easily degraded in the organism, so when using peptides as targeting units for exosomes, the stability factor needs to be taken into account to avoid that the exosome-targeted drug delivery vehicle does not achieve the desired effect in the organism.
- CART exosomes
By replacing the variable region of T cells with single-chain antibodies through gene editing techniques, chimeric antigen receptors (CARs) are expressed on the surface of T cells. The single-chain variable fragment (scFv) or ligand in CARs provides antibody-like specificity to T cells, allowing them to bind to target cells expressing the corresponding antigen, resulting in chimeric antigen receptor T cells. It mainly uses nanocarriers to deliver cytotoxic drugs or vaccines to TAFs with high efficiency to achieve selective killing of TAFs, alleviate the tumor suppressive microenvironment, increase the penetration of anti-tumor drugs, and promote the activation and infiltration of immune cells.
Note: The key strategies we focus on are always up to date, please contact us by email for more up-to-date and relevant information.
Alfa Oncology is committed to supporting scientists in making breakthrough scientific discoveries and developing new applications to accelerate new drug discovery and scientific diagnosis and treatment. Our high-performance scientific instruments and high-value solutions enable scientists to explore the mysteries of life at the tumor microenvironment level. Please tell us your project requirements, and we will provide you with a full service from solution to report. If you have any questions, please feel free to contact us.
- Dai J, Su Y, Zhong S, et al. Exosomes: key players in cancer and potential therapeutic strategy[J]. Signal Transduction and Targeted Therapy, 2020, 5(1).