Experimental pre-treated leukemia cells double the immune response in mice after chemotherapy

An experimental pre-treated leukemia cells double the immune system response in mice after chemotherapy, according to a study led by the University of Miami Miller School of Medicine. The study was conducted while testing new anti-tumour immunotherapy regimens for a rare form of leukemia. The research was published in the journal Nature Communications.

“LA-Hepatocellular leukemias can occur, but they are rare and hard to treat. In 2017 we reported a clear increase in mortality from the rare disease of 30 to 41% in patients with advanced head and neck lymphoma, which were primarily treated with anti-PD-1 immunotherapies,” said Manoj Anand, M.D., a professor of Radiation Oncology at the Miller School of Medicine and senior investigator on the study.

In this study, the mice received a programmed remission (PD) therapy, an immunotherapy treatment that immunizes animals against malignant cells. Like other therapies, PD immunotherapies cause a stronger immune system response, allowing a full checkpoint blockade to be enjoyed in patients. The PD immunotherapies are currently being used to treat patients with glioblastoma, a neuroblastoma which occurs in the brain and spinal cord and can be extremely difficult to eradicate.

In this study, the researchers compared modification therapy regimen, which is a systemic immuno-suppressive regimen, to an oral regimen, expertly treated with recombinant T-cells that express CD15-3 or CD15-4. The PD care regimens were infused into mice after initial chemotherapy with a CD15-3 or CD15-4 inhibitor.

“The epithelial progression of the lesion was significantly reduced,” Anand said.

Dr. Anand and his team observed no tumors detected in their mice while orally administered chemotherapy.

To evaluate the immunoregulatory effect on leukemia cells in mice, the researchers treated the mice with antibodies that bind and neutralize CD15-3 or CD15-4 expression. The antibodies that bind to and neutralize CD15-3 or CD15-4, blocks CD15-3 and CD15-4 expression, thereby protecting leukemia cells. Among the mice given PD therapy, only T cells with CD15-4 expression survived at least ten months without stimulation.

“Our immunotherapy regimen provides a new strategy for treating Morbus C therapy-induced leukemia,” said Manoj Anand, their senior author and Director of the Miller School.

“Immunotherapy is a treatment path that has, until now, not been designed. Although immunotherapy is new, it is being investigated as a potential approach to treat chronic leukemia, which is not curable and is often recurred after standard chemotherapies, including PD-1 therapy,” he said.

“Our study is important for the discovery of this potential strategy to treat CD15-3 and CD15-4 leukemias in order to relieve the suffering of patients and reduce relapse and progression,” said Dr. Anand.