Unlocking Cancer’s Weakness: How Scientists Are Targeting Mesothelin

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.

 

Similar Posts

  • | |

    Doctors Describe "Concrete Therapeutic Approach" for Mesothelioma

    A team of medical researchers in Italy have achieved what they are calling “excellent” tumor control and survival results in malignant pleural mesothelioma patients using a combination of surgery, chemotherapy, and radiotherapy. Caused by exposure to asbestos, mesothelioma typically spreads quickly across the lung-encasing membrane called the pleura. There is no known cure but treatments are improving. In the current prospective study, 20 malignant pleural mesothelioma patients underwent radical pleurectomy/decortication followed by high doses of radiation. After surgeons removed as much of the visible mesothelioma tumor and surrounding tissue as possible, patients received 50Gy of radiation to the effected side of their chest, delivered in 25 fractions. Regions of particular concern for mesothelioma regrowth got an extra radiation “boost” to…

  • | |

    Does Radiotherapy Reduce Mesothelioma Pain?

    A new study says there is not enough evidence to support the use of radiotherapy for the treatment of pain associated with malignant pleural mesothelioma. Researchers at the University of Edinburgh in Scotland reviewed a range of past studies on mesothelioma pain and radiotherapy by searching databases that date back as far as 1974. To be eligible to be included in their review, the study had to focus on malignant pleural mesothelioma and radiotherapy given “with the intent of improving pain”. The study also had to report doses and fractionation of the radiotherapy and how the pain responded. In all, the researchers found eight studies on mesothelioma pain and radiotherapy that met the criteria. Two of the studies were prospective…

  • | |

    Radiotherapy for Mesothelioma: Better But Still Limited

    A form of highly-targeted radiation therapy for mesothelioma is better than it used to be, but is still risky. That is the message of a recent article on intensity-modulated radiation therapy (IMRT) in Seminars in Thoracic and Cardiovascular Surgery. Author Kenneth E. Rosenzweig, MD, a Radiation Oncologist with Mount Sinai Hospital in New York, reviewed recent studies on IMRT and mesothelioma. He concludes that, while the “troubling toxicity” associated with IMRT when it was first introduced has not been entirely eliminated, the fact that clinicians now have more experience with it is making a positive difference for mesothelioma patients. Before targeted therapies like IMRT were available, high-dose radiation was not usually a feasible option for mesothelioma since the irregular shape…

  • | |

    A Second-Line Option for Mesothelioma?

    Although survival was not significantly extended, the chemotherapy drug vinorelbine might be a treatment option for mesothelioma patients whose cancer has returned after first-line chemotherapy with pemetrexed. A new study on vinorelbine as a second-line treatment finds that the drug is “moderately active” in mesothelioma patients who were initially treated with pemetrexed-based chemotherapy. Pemetrexed (Alimta), along with a platinum-based drug like cisplatin, is the primary first-line drug therapy for mesothelioma. But vinorelbine is gaining attention as a possible option for mesothelioma, in part because it is available in a less expensive generic form. In “Vinorelbine in pemetrexed-pretreated patients with malignant pleural mesothelioma”, the Italian authors detail the results of their study on 59 patients with unresectable pleural mesothelioma.  These patients…

  • | |

    Repeat HIPEC Improves Mesothelioma Survival

    If one cytoreductive surgery and HIPEC procedure for mesothelioma is good, subsequent treatments may be even better. That is the central message of research conducted at the Moffitt Cancer Center in Florida. The study’s aim was to assess overall survival among peritoneal mesothelioma patients who had not just one, but two or more rounds of heated intraperitoneal chemotherapy (HIPEC) after cytoreductive surgery. The cytoreduction/HIPEC approach has become popular for peritoneal mesothelioma, a treatment-resistant cancer of abdominal membranes caused by asbestos. Cytoreductive surgery involves removing as much of the mesothelioma tumor as possible from the abdomen. Because the shape and spreading pattern of mesothelioma tumors make complete cytoreduction difficult, the surgery is often followed by a rinse with a heated solution…

  • | |

    Value of Mesothelioma Surgery Challenged for Healthy Patients

    New research conducted in Italy and presented at the 15th World Conference on Lung Cancer in Sydney, Australia suggests that mesothelioma surgery – no matter what kind – may not offer a survival advantage over medical management for the healthiest of patients. Mesothelioma is a rare but aggressive malignancy that is highly resistant to standard cancer treatments. The two types of mesothelioma surgery considered to be options for people with resectable cancer are pleurectomy decortication (P/D) or extrapleural pneumonectomy (EPP). While EPP is more radical than P/D because it involves removing a lung, both carry a heavy risk of complications and, according to the Italian researchers, may not be of value for certain patients. The study reviewed data from 1,365…