Katy Rezvani (M.D. Anderson Cancer Center)
6 Feb. 2020. A small-scale clinical trial shows most patients with two blood-related cancers safely respond to immune system cells derived from umbilical cord blood. Researchers from M.D. Anderson Cancer Center in Houston, part of the University of Texas system, report their findings from patients with relapsed or refractory non-Hodgkin lymphoma and chronic lymphocytic leukemia in today’s issue of the New England Journal of Medicine (paid subscription required).
A team from the M.D. Anderson lab of stem cell researcher Katy Rezvani is seeking new methods for treating patients with blood-related cancers using engineered T-cells from the immune system. Up to now, most of these treatments genetically modify a patient’s own T-cells, by adding chimeric antigen receptor proteins, which when added to T-cells — known as CAR T-cells — are strong cancer cell killers.
CAR T-cell therapies reprogram the T-cells with genetic engineering to find and kill cancer cells like an antibody. These modified T-cells are infused back into the patient, seeking out and binding to a protein called CD19 found on the surface of B cells — another type of white blood cell — associated with several types of blood-related cancers. But these treatments also produce severe adverse effects in many patients, which limits their utility and forced the stoppage of some clinical trials. As reported by Science & Enterprise in September 2017, these continuing problems required development of special guidelines for using CAR T-cells, led by two co-authors of the new paper, Elizabeth Shpall and Sattva Neelapu.
In the new study, Rezvani and colleagues tested another type of immune-system cells known as natural killer cells, which in their normal state are avoided by cancer cells. As with CAR T-cells, the researchers add chimeric antigen receptors to natural killer or NK cells to produce CAR-NK cells. The team’s CAR-NK cells are bolstered with interleukin-15, a protein that regulates and promotes immune cell growth, and caspase-9, an enzyme that induces cell death, added as a safety switch.
In addition, the researchers derived their natural killer cells from umbilical cord blood donated by parents after their child’s birth. Umbilical cord blood is a rich source of stem cells that can be harvested for therapies. M.D. Anderson collects these donations in a cord blood bank for research and treatments.
The early- and mid-stage clinical trial is testing CAR-NK cells in patients with B-cell cancers: non-Hodgkin lymphoma, chronic lymphocytic leukemia, or acute lymphocytic leukemia. The study is looking primarily at the safety of the treatments, watching for signs of adverse effects, as well as gauging the optimum CAR-NK cell doses. But the trial is also assessing patients’ clinical responses to CAR-NK cells, in terms of disease remission and survival, at least 30 days after infusion.
The paper reports on 11 patients treated with CAR-NK cells, six with non-Hodgkin lymphoma and five with chronic lymphocytic leukemia. Seven of the 11 participants (63%) achieved complete remission from their disease and another patient showed partial remission, which occurred within 30 days following their treatments. The seven patients with a complete response remained free of their disease for a median of nearly 14 months after infusion.
In addition, no patients showed evidence of adverse effects associated with CAR T-cell treatments including cytokine release syndrome, toxicity to nerve cells, or graft-versus-host disease, nor any increases in inflammatory proteins. Adverse effects were found in some patients from the chemotherapy given before the CAR-NK treatments, which Rezvani says were resolved within two weeks, and did not require intensive care for any patients.
Cord blood stem cells can be collected and banked from donors for future use by any patients, thus stored and used off-the-shelf. “Due to the nature of the therapy,” notes Rezvani in an M.D. Anderson statement, “we’ve actually been able to administer it in an outpatient setting.” CAR T-cells, on the other hand, are derived from a patient’s own T-cells in most cases, then regenerated in a process taking several weeks.
In November 2019, Takeda Pharmaceutical Company in Tokyo gained an exclusive license to M.D. Anderson’s CAR-NK technology. The deal covers four clinical targets for the treatments, with M.D. Anderson receiving initial and milestone payments, as well as royalties on sales, while Takeda is responsible for further development, manufacturing, and commercialization. Financial terms were not disclosed.
More from Science & Enterprise:
- FDA Clears Placenta Cell Brain Cancer Trial
- Synthetic Bio Cancer Immunotherapy Company Acquired
- Engineered Viruses Licensed for Cancer Therapies
- T-Cells Engineered to Release Anti-Cancer Proteins
- MD Anderson, Biotech Partner on T-Cell Receptors
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