Health
Antibody-peptide-inhibitor conjugates: a new avenue for cancer treatment
“Tumor cells often hijack normal physiological processes to promote their growth and exploit proteins that serve important cellular functions. It is therefore important to inhibit the activity of these proteins only in cancer cells, without affecting their vital roles in healthy tissues. For this reason, traditional approaches using small molecules that cause systemic inhibition in all cells in the body can cause serious side effects.”
Examples of essential proteins that are hijacked by cancer cells include cathepsins, a family of enzymes responsible for breaking down other proteins and rebuilding body tissues. Cathepsins have been implicated in a variety of cancers, osteoporosis, and autoimmune diseases. However, clinical trials with small molecule inhibitors of cathepsins have failed due to lack of efficacy or toxicity.
Now, a team of scientists led by Elisa Oricchio and Bruno Correia at EPFL has developed a new approach that overcomes these limitations: They created a modular drug platform that conjugates non-natural peptide inhibitors (NNPIs) with antibodies to create antibody-peptide-inhibitor conjugates (APICs). This method allows the inhibitors to be delivered specifically to cancer cells, reducing systemic side effects and improving the efficacy of treatment.
The researchers started by designing an NNPI that would covalently bind and inhibit cathepsins. They modified the peptide sequence to include a Michael acceptor, a chemical moiety that makes it easier to form a stable bond with cathepsins.
The Michael acceptor reacts with a cysteine residue in the active site of cathepsins (the part of the enzyme that performs the main function) to form a stable covalent bond that effectively inhibits cathepsins. To further optimize the specificity and potency of their peptides, the team used saturation mutagenesis screening, a method in which each amino acid in a protein is systematically altered to find the optimal variant with the desired properties.
The researchers identified several potent inhibitors against four different cathepsins: cathepsin S, B, K, and L. By conjugating these inhibitors to antibodies that recognize CD22, CD79, HER2, and Siglec15, the researchers were able to precisely deliver the NNPI to lymphoma cells, breast cancer cells, and osteoclasts, leveraging the natural ability of antibodies to be internalized into target cells, directing the inhibitors exactly where they are needed.
Next, we put APIC to the test. In both cell lines and animal models, APIC showed remarkable therapeutic effects. For example, in a lymphoma model, treatment with APIC targeting cathepsin S shrank tumors and activated an immune response against cancer cells. In a breast cancer model, APIC targeting cathepsin B inhibited tumor invasion and cell migration, highlighting the potential of APIC to prevent metastasis.
By specifically delivering inhibitors to cancer cells, the APIC approach avoids or minimizes the side effects commonly seen with other treatments such as chemotherapy. Furthermore, the modular nature of the APIC design allows it to be tailored to target different proteases involved in different diseases, potentially revolutionizing the therapeutic landscape for diseases other than cancer.
The APIC project has now moved beyond the lab and taken its first steps towards clinical reality. “We have filed two patents based on this project,” says Elisa Oricchio. “Aaron Petruzzella, the PhD student who led the project, has recently been supported by an SNF Bridge Proof-of-Concept Fellowship to continue working on these inhibitors, laying the groundwork for a start-up and attracting the attention of potential investors.”
|
Sources 2/ https://www.sciencedaily.com/releases/2024/05/240529144045.htm The mention sources can contact us to remove/changing this article |
What Are The Main Benefits Of Comparing Car Insurance Quotes Online
LOS ANGELES, CA / ACCESSWIRE / June 24, 2020, / Compare-autoinsurance.Org has launched a new blog post that presents the main benefits of comparing multiple car insurance quotes. For more info and free online quotes, please visit https://compare-autoinsurance.Org/the-advantages-of-comparing-prices-with-car-insurance-quotes-online/ The modern society has numerous technological advantages. One important advantage is the speed at which information is sent and received. With the help of the internet, the shopping habits of many persons have drastically changed. The car insurance industry hasn't remained untouched by these changes. On the internet, drivers can compare insurance prices and find out which sellers have the best offers. View photos The advantages of comparing online car insurance quotes are the following: Online quotes can be obtained from anywhere and at any time. Unlike physical insurance agencies, websites don't have a specific schedule and they are available at any time. Drivers that have busy working schedules, can compare quotes from anywhere and at any time, even at midnight. Multiple choices. Almost all insurance providers, no matter if they are well-known brands or just local insurers, have an online presence. Online quotes will allow policyholders the chance to discover multiple insurance companies and check their prices. Drivers are no longer required to get quotes from just a few known insurance companies. Also, local and regional insurers can provide lower insurance rates for the same services. Accurate insurance estimates. Online quotes can only be accurate if the customers provide accurate and real info about their car models and driving history. Lying about past driving incidents can make the price estimates to be lower, but when dealing with an insurance company lying to them is useless. Usually, insurance companies will do research about a potential customer before granting him coverage. Online quotes can be sorted easily. Although drivers are recommended to not choose a policy just based on its price, drivers can easily sort quotes by insurance price. Using brokerage websites will allow drivers to get quotes from multiple insurers, thus making the comparison faster and easier. For additional info, money-saving tips, and free car insurance quotes, visit https://compare-autoinsurance.Org/ Compare-autoinsurance.Org is an online provider of life, home, health, and auto insurance quotes. This website is unique because it does not simply stick to one kind of insurance provider, but brings the clients the best deals from many different online insurance carriers. In this way, clients have access to offers from multiple carriers all in one place: this website. On this site, customers have access to quotes for insurance plans from various agencies, such as local or nationwide agencies, brand names insurance companies, etc. "Online quotes can easily help drivers obtain better car insurance deals. All they have to do is to complete an online form with accurate and real info, then compare prices", said Russell Rabichev, Marketing Director of Internet Marketing Company. CONTACT: Company Name: Internet Marketing CompanyPerson for contact Name: Gurgu CPhone Number: (818) 359-3898Email: [email protected]: https://compare-autoinsurance.Org/ SOURCE: Compare-autoinsurance.Org View source version on accesswire.Com:https://www.Accesswire.Com/595055/What-Are-The-Main-Benefits-Of-Comparing-Car-Insurance-Quotes-Online View photos
to request, modification Contact us at Here or [email protected]
 |
 |
 |
