Novel way to make immunotherapy work for lymphoma

Researchers have found a novel way to use immunotherapy drugs against treatment-resistant cancer that starts in white blood cells called lymphocytes, by combining them with stem cell transplantation.

The approach, described in the journal Cancer Discovery, also dramatically increased the success of the drugs in melanoma and lung cancer.

This type of immunotherapy, called "checkpoint blockade," ramps up the ability of immune cells called T cells to fight cancer by removing the "cloaking effect" that tumours use to hide from them.

Checkpoint blockade therapy is effective in several tumour types, but generally ineffective in non-Hodgkin's lymphomas, said researchers from the Mount Sinai Hospital in the US.

However, the study found that when this immunotherapy is combined with a stem cell transplant, which the researchers call "immunotransplant," the process ramps up the T cells to increase the cancer-killing immune response tenfold.

This allows the therapy to be effective for non-Hodgkin's lymphoma and more successful for melanoma and lung cancer.

The transplant works by "making space" for re-infused immune cells (T cells) to proliferate by clearing out a patient's original immune system.

While they are proliferating and building the immune system back up, they become activated, and the anti-tumour T cells' anticancer effect becomes stronger.

The findings have prompted the initiation of a clinical trial using the immunotransplant approach to treat patients with aggressive non-Hodgkin's lymphoma.

They also could eventually lead to effective therapies for other cancer types, researchers said.

"Using immunotransplant to enhance the efficacy of checkpoint blockade therapy could be broadly significant as these immunotherapies are a standard therapy for melanoma, kidney cancer, lung cancer, and others," said Joshua Brody, from Mount Sinai Hospital.

"Even for settings in which checkpoint blockade therapy proves ineffective, our data suggest that its efficacy may be 'rescued' by immunotransplant.

"This research also suggests that the addition of checkpoint blockade may improve other T cell therapies, such as CAR-T therapy," Brody said.

Researchers based their findings on their observation of how the immune system responded to bone marrow transplants, T cell therapy, immunotherapy, and immunotransplant in patients and mouse models.