Car t cell therapy is one of the most promising new cancer treatment to emerge in recent years. It involves removing a patient’s own immune t cells and engineering them to recognize specific targets on the surface of the cancer cell.

A Major Limitation of this type of car t cell therapy, called autologist therapy, is that the cells are taken from the patient and must be custom-made into a treatment. This requires patients to wait until their cells are modified for Infusion – princess time they may not have.

Now Research Done At Memorial Sloan Keettering Cancer Center (MSK) S . The research identifies a way to modify the donor car t cells, called allogenic car t cells, so that they won’t be rejected by the patient receiving from and will personal person

The new approach involves equipping the car t cells with a protein called nef. The researchers showed that inserting nef into donor car t cells enabled the cells to survive and remain potent in a mouse model for cancer.

“This could be an important step toward creating safe and effective allugneic car t cells, which would be greatly increased the number of patients who could beefit from,” Arlo Perica, MD, Ph.D., The Study’s First Author.

The research, Published in NatureWas conducted in the laboratory of Michel Sadelain, MD, Ph.D., Who is a Pioneer of Car T Cell Therapy. Dr. Sadelain Left Msk in Fall 2024.

Using Viruses to Study How Cells Can Evade Immune Attack

The research builds upon important technical advanas made in the sadlain laboratory in recent years. The scientists knew that viruses had an array of tools to evade or withstand immune attack after entering the body and infecting cells. (When a virus invades a cell, it must keep the cell alive long enough for the virus to make copies of itself using the cell’s machineinery.)

“We wanted to learn which components of the immune system might cause rejection of donor car t cells, and how difference is Viral Proteins Could Figure Out aR ARAND THAT,” Dr. Perica says. “We thinkt that these viruses, which have been invading cells for Millennia, would have somewithing to teach us about avoiding immune detection and keeping the cells that they invades that they invade alive.”

To identify the viral protein providing the most protection, the resultarches employed advanced tools developed in the sandelain lab. By using a Gene-Editing tool Called Crispr, They Blad Insert Different Viral Proteins at a Precise Region in the Genome of the Car T Cell Call Called The Tracks.

Car t cells made in this fashion have some remarkable properties. They maintain their cancer-Fighting ability for a long time. In addition, inserting a protein at the trac locus replaces a receptor that can cause a donor t cell to attack the recipient’s tissue – What is Known as Graft vs. Host disease.

The researchers are tested the different car t cells in a mouse model that contained human immune cells, making it possible to see then which is the VILILSINE Equipped the Cells to Best Survive in this Setting.

Nef helps car t cell survival

The clear winner was a protein called nef, which is used by the HIV Virus to Evade Detection by the Immune System. It worked in two ways: First, it reduced a protein called Hla-I on the surface of the car t cells. Hla-I normally serves as a red flag to the immune system, Signaling that someone is wrong and inviting attack-insupping hla-i helped the cell story undetected. In addition, nef helped prevent a form of cell suicide called apoptosis in the car t cell.

“Theose two mechanisms combined showed that nef is uniquely suited to create a powerful allogenic car t cell,” Dr. Perica says.

The hope is to begin testing these car t cells in clinical trials at some point. Off-the-shhelf car t cells are alredy being tested at msk to treat multiple myeloma, although that treatment requires immune-supppressing drugs as part of the therapy. This New Advance could potentially create off-the-shelf car t cells that do not need Deep Immune Suppression, Whoch Comes with An Increated Risk of Side Effects Such as Infections.

The Benefits of Donor Car T Cells

Allgeneic car t cells even additional adhvantages for fighting cancer. Cancer Patients Tend to Be Older and Have Often Received Treatments By Contrast, Allgeneic T Cellsqu Come from Donors Who are Youner and Healthier, Making the modified cells more likely to survive after infusion.

“The Multiple Discoveries Coming out of Dr. Sadelain’s Lab Have Helped Bring Us Closer to the day when we have car t cells right at hand to give to patients with delay,” Perica says. “Removing the need for manufacturing personalized car t cells would make the treatment much more widely available and more affordable.”