Synthetic antibody – immune cell complex significantly reduces hematomas | Science

New Orleans-The donated immune cells were mixed with a molecule that helps them return to the cancerous cells, dramatically shrinking tumors in most of the 22 people with leukemia who received the trial infusions. The findings, announced yesterday at the annual meeting of the American Association for Cancer Research (AACR), are a new development in cellular therapies that harness a patient’s immune cells to treat cancer. Study leaders say the new treatment is easier than other cellular treatments for advanced lymphoma, or cancer of the lymphatic system.

“It’s an interesting idea,” says hematologist and oncologist Jeffrey Miller of the University of Minnesota, Twin Cities, who was a member of the plenary session where the work was presented.

CAR-T cells, which are immune cells genetically modified to carry a surface protein that helps them return to cancer cells, are the best known treatment for cancer cells. Although approved for some types of leukemia and lymphoma, CAR-T cells can cause serious side effects and must be made specifically from an individual’s own T cells.

To formulate a more gentle and practical alternative, some researchers are supplementing a different type of immune cell, natural killer (NK) cells, with the surface protein. Known as the chimeric antigen receptor (CAR), it binds to a tumor cell surface protein, or a marker that identifies a cell as cancerous. Unlike CAR-T cells, these cells can be harvested from donated blood, either from an adult donor or umbilical cord blood, and do not provoke a dangerous immune response if transferred to another person.

But genetically engineering CAR cells is expensive and complex. In short, scientists are creating protein drugs called bispecific antibodies. These antibodies have two arms, one that attaches to the T cell or natural killer cell and the other to the tumor marker. When infused into a patient, the antibody binds to the two cells so that the immune cell attacks the tumor just as the CAR cell would.

One such bispecific, called AFM13, binds NK cells to a marker called CD30 on Hodgkin’s lymphoma cells. But the antibody, produced by biotech company Affimed, has not worked well in patients so far. Hematologist-oncologist Katie Rezvani at the MD Anderson Cancer Center and her colleagues thought the problem might be in the patient’s NK cells: They were simply too weak to function, compared to a healthy person’s cells. So her team tried mixing AFM13 in a lab dish with normal, donated NK cells. They added a blend of proteins called cytokines to boost their effectiveness. “It was a simple idea,” says Rezvani. But the NK cell-antibody complex was successful in shrinking tumors in mice.

They then tested this strategy on 22 people with Hodgkin lymphoma who had relapsed after several different treatments. Patients first received a few days of chemotherapy to deplete their NK cells and make room for the donated cells. They then received an injection of AFM13-coated cells isolated from umbilical cord blood. As the bispecific antibody drops from the NK cell within a few days, they also received weekly infusions of AFM13. A month later, they received a second dose of AFM13-NK cell therapy with cells from a different cord blood donor.

The circulating natural killer cells in AFM13 remain the same for about 3 weeks before a person’s immune system eliminates them. “But those three weeks are enough for a good response. We are seeing massive tumor lesions shrink within a day,” says oncologist Iago Nieto, who presented the work at the AACR meeting. None of the patients experienced serious side effects, and tumors shrank in 17 of 19 patients could be evaluated.Of the 13 people who received the three highest doses of natural killer cells, tumors completely disappeared in eight cases.

Radwani says a woman in her fifties was going to a shelter and could barely walk when she joined the trial. But after the treatment, the researcher noted, she “came out of the ward to live a very normal life.”

Although some tumors resumed growth, of the 13 patients with high doses, seven remained in remission after 5 to 11 months. Without treatment, Netto says, many would have died in that period. Two were healthy enough to have a stem cell transplant, which could treat the disease. The team hopes that with repeated treatments with the antibody-coated NK cells — they plan to increase the number of cells to four — the combination alone might be enough to shrink tumors for years.

Miller calls the work a “good study” and says this approach could make it easier to stock natural killer cell therapies so that they are ready for patients more quickly. But he adds that it is difficult to separate the effects of the antibody-treated cells from the direct injection of AFM13 patients at a later time. He is also cautious about whether treatment will keep tumors under control in the long term.

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