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New Cell-Based Immunotherapy Shows Positive Results in Initial Trial on Blood Cancers

New Cell-Based Immunotherapy Shows Positive Results in Initial Trial on Blood Cancers
02/11/2020
forbes.com

Forbes.com

A new cell-based immunotherapy for some types of blood cancer has posted promising initial results in a small clinical trial on patients who had exhausted all other treatment options.

The new study, led by researchers from MD Anderson Cancer Center was published yesterday in the New England Journal of Medicine and used a type of immune cell, called a Natural Killer (NK) cell. The NK cells were engineered to target a protein called CD19 found on B-lymphoblasts and which can become cancerous and cause several types of blood cancer. The study tested the treatment on 11 patients with either chronic lymphocytic leukemia (CLL) or non-Hodgkins lymphoma (NHL), finding a 73% response rate. Of the 8 people who responded, 7 maintained a complete response over a year after the initial treatment.

“All our patients had failed conventional therapies and therefore there was no alternative treatment available for them,” said Katy Rezvani, M.D., Ph.D., lead author of the paper and professor of Stem Cell Transplantation & Cellular Therapy at MD Anderson. “We are encouraged by the results of the clinical trial, which will launch further clinical studies to investigate allogeneic cord blood-derived CAR NK cells as a potential treatment option for patients in need,” she added.

Most cell-based therapies use a different type of modified immune cell; CAR T-cells. These therapies have shown initial promise in some types of blood cancer, but there have been several setbacks with side-effects in patients and the scalability and cost of the technology. Importantly, the NK cells used on the patients in the new study were made from donated umbilical cord blood, whereas most CAR T-cell therapies currently rely on a long and expensive process of extracting T-cells from the patient themselves, genetically modifying them and expanding the cells before the therapy is ready for use.

This means the new NK cell therapy can theoretically be produced in bulk and doesn't rely on extracting T-cells from the patient, which can be incredibly difficult, especially if the patient has received a lot of previous therapies which can affect T-cell numbers.

“Strictly speaking, the manufacturing and engineering steps for CAR T and CAR NK cells are very similar. The main difference is that unlike commercial CAR T-cells, where one product is used to treat one patient (an autologous product), CAR NK cells are not patient-specific, allowing for multiple doses to be manufactured from one donor that can then be used to treat multiple patients,” said Rezvani.

CAR T-cell therapies, although posting some wonderful results, particularly in children with hard-to-treat, relapsed leukemias, do come with a lot of side effects, particularly neurotoxicity and cytokine release syndrome, which is life-threatening if not quickly treated. These toxicities were not seen in this initial, small trial, giving the researchers hope that perhaps this therapy may have fewer serious side-effects than other similar approaches.

As well as CAR T-cells, there is also another therapy already available which targets CD19, a drug called blinatumomab (Blincyto). What potential advantages does the new NK cell therapy have over this approach?

“These are living cells that persist after infusion and will potentially continue to protect the patient from their cancer over time unlike blinatumomab that needs to be given as a continuous infusion and in multiple cycles,” said Revzani. “In addition, with the caveat of the small number of patients that we have treated so far and the relatively short follow up time, our approach appears to be less toxic,” she added.

MD Anderson has licensed the development of this therapy and other similar B-cell targeting therapies to company Takeda Pharmaceuticals.

“Our vision is to improve upon existing treatments by developing armored CAR NKs that could be administered off-the-shelf in an outpatient setting—enabling more patients to be treated effectively, quickly and with minimal toxicities,” said Rezvani, adding that the team also plans to expand the trial to encompass other CD19-expressing malignancies such as B-cell leukemias.

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