Unlocking Cancer’s Weakness: How Scientists Are Targeting Mesothelin

When it comes to fighting cancer, scientists have been working hard to find better ways to help patients. One exciting area they’re exploring is something called CAR-T therapy, which targets specific proteins found on cancer cells.

One of these proteins, called mesothelin, is found in different kinds of cancer like mesothelioma, ovarian, lung cancer, and some types of leukemia. But using CAR-T therapy against mesothelin has been tricky. The treatment sometimes gets tired out, and other proteins in the body can stop it from working well.

To fix these problems, scientists have come up with a new way to make CAR-T therapy work better against mesothelin in cancer.

Game-Changing Journey to Success

First off, they made a special kind of CAR that’s fully human and uses a smart technology called OutSpacer. This special CAR is like a key that can lock onto mesothelin on cancer cells. But here’s the cool part: they made sure this key works super well by tweaking its shape and design using this OutSpacer technology.

They tested over 300 different keys (or CARs) in the lab to see which one works best. These tests checked if the CARs could kill cancer cells and make helpful chemicals without being stopped by other proteins in the body.

The found the best key, called B8S8, was a real superhero! It could wipe out cancer cells even with fewer teammates compared to other keys.

But they also found a way to make these CAR-T cells stay strong for longer. They used a smart trick called a “stim-on” promoter (OP1) that helps the CAR-T cells stay powerful and keep making those helpful chemicals. This made a big difference because CAR-T cells using this trick were better at fighting cancer compared to others that didn’t have this trick.

Bright Prospects for Patients

All these discoveries mean good news for people fighting cancers with mesothelin. The scientists found out that these special keys can be even better than they thought. They don’t get stopped by other proteins, and they stay strong against cancer for a longer time.

Scientists are getting closer to a better way to fight certain cancers, including mesothelioma. This new way might help lots of people in the future, and it’s a step forward in finding better treatments for cancer.

It’s exciting to see how science keeps moving forward to help people beat cancer. And who knows, with more discoveries like these, we might just find a way to make cancer a thing of the past!

Source:

Yokoyama, Jason, Allan Wang, Maria Steele, John Crowl, Thaddeus Davenport, Jared Hammer, Willimark Obenza, et al. “Development of a Regulated, Optimized Mesothelin Chimeric Antigen Receptor (CAR) for the Treatment of Mesothelin Positive Cancers.” Blood 142 (November 28, 2023): 3461. https://doi.org/10.1182/blood-2023-190321.