A Lethal Tailor Outfits Cancer-Hunting T-Cells: How It Works

(Bloomberg) — For decades, doctors have treated cancer by direct assault. Surgeons cut away a tumor or remove a breast. Doctors beam radiation to destroy the fragile DNA of malignant cells. Chemotherapeutic drugs poison a cancerous growth.

A new generation of treatments, now being tested in blood cancers, uses a roundabout approach. Doctors administering the therapy, called CAR, for chimeric antigen receptor, remove and modify the body’s defenders, the T-cells that attack invasive bacteria and viruses, and re-tailor them to hunt down cancers of the blood.

It’s not a simple process. Patients give a blood sample and technicians in a lab isolate the killer T-cells within. The T- cells are then “infected” with an inactivated virus that carries genes designed to recognize cancer cells, called a receptor. The T-cells are now primed to find cancer, acting like a magnet to pull the immune system into hand-to-hand combat with cancer cells circulating in the blood.

Once technicians have modified the cells in the lab into bespoke cancer hunters, they’re bathed in growth-promoters, which cause them to replicate until there are billions of copies. The patient gets chemotherapy to kill some of the existing immune and cancerous cells, and the engineered versions are infused back into the body. They become part of the normal immune system, only now specially programmed to go after the malignant blood cells crowding the patient’s circulatory system.

With their specially engineered receptors, they hunt down and latch on to malignant cells, sounding an alarm that sends molecules to drill a hole in the offending cell and insert proteins that cause it to dissolve.

Tailored Killers

For now, the tailored technology only works on blood cancers, where malignant cells circulate through the body, putting them in close proximity to the T-cells. Many blood cancers are perversions of what are known as B-cells, a circulating part of the immune system that makes antibodies.

When B-cells turn malignant, they grow too quickly and remain immature, failing to work properly. Patients may be tired and feverish, with pale skin and frequent bruises. The condition can cause frequent infections and it’s normally diagnosed after a physical exam and blood test that shows abnormal cells.

The CAR products now in development by Juno Therapeutics Inc., Bluebird Bio Inc., Novartis AG and others target a protein found only on B-cells, wiping them out. People can live without B-cells, and it’s possible that when they return after treatment they may no longer be damaged.

Solid tumors — killers like lung cancer, melanoma, breast cancer and others that make up 90 percent of cancers — will be harder to attack. The solid tumors don’t have a unique target on the outside of the cell, one that T-cells could pinpoint. Instead, the proteins found on those tumors are typically present in many cells throughout the body, and attacking them would cause widespread collateral devastation.

The hunt is still on for an appropriate target.

–With assistance from Caroline Chen in San Francisco.

To contact the reporter on this story: Michelle Fay Cortez in Minneapolis at [e-mail] To contact the editors responsible for this story: Crayton Harrison at [e-mail]