Tethered stem cells and platelets can help us escape cancer, say UCLA scientists. In the new study of the scientists, the cancer is leukemia. Defiant cancers include a guide, a hematopoietic stem cell (HSC), and a drug carrier, a constructed platelet. The guide brings the duo to the bone marrow, and the drug carrier provides checkpoint inhibition therapy.
In experiments with mice that had acute myeloid leukemia, the UCLA team noted that their unusual combination therapy was stopping the disease from developing further. Of the treated mice, 87.5 percent were cured 80 days after injection of the combination cells. These mice were also all resistant to leukemia cells re-injected two months after the 80 day period.
Further details appeared on October 29, in the journal Nature Biomedical Engineering in an article entitled, "The Conjugation of Hematopoietic Stem Cells and Platelets Decorated with Anti-PD-1
"After intravenous injection into mice carrying leukemia cells, the HSC platelet migrated -aPD-1 conjugate released into the bone marrow and local aPD-1, significantly increasing immune responses to leukemia and increasing the number of active T cells , the production of cytokines and chemokines as well as the survival time of the mice are increased, "stated the authors of the article. "This cellular conjugate also promoted resistance to relapse with leukemia cells."
This unusual immunotherapy approach could be used with other therapies, such as chemo and stem cell treatment, to improve their efficacy, "said the senior author, Zhen Gu, Ph.D. Professor of Bioengineering at UCLA's Samueli School of Engineering. Gu added that the method would need to be tested and approved in human clinical trials before it can be used in the treatment of people with leukemia.
Acute myeloid leukemia is a cancer that begins and can spread in the bone marrow Blood circulation and other parts of the body In a weakened immune system, a person with this type of leukemia may die from complications from other diseases.
Chemotherapy alone is moderately effective in treating leukemia: leukemia does not occur in about 1 in 3 patients in remission on patients after chemo as specified n the American Cancer Society. About half of the diseased people can relapse, typically within two years of treatment, usually because chemotherapy can not reach cancer cells in the bone marrow.
The UCLA-led research aimed to solve this problem by developing a method to deliver drugs directly into the bone marrow. The approach called "cell combination drug delivery" is the first to link two different cells together for therapeutic purposes.
"This platelet part of the cell combination is like a delivery van," Dr. Gu. "We can package and activate drugs or immune system boosters on the cell surface of platelets to discharge them once at the target site in the body."
The HSC portion of the cell combination can find its way into the bone marrow through specific chemical signals. "The hematopoietic stem cells are like a target signal for the bone marrow," commented Quanyin Hu, Ph.D., a lead author of the newspaper and a former Ph.D. Gu. "Once the stem cells have delivered the combination cells into the medulla, the platelets can be activated, releasing immune cell loadings in the medulla to support the body's defenses, in this case T cells, to kill leukemia cells."
The researchers said they intend to further explore the approach as a possible treatment for leukemia and other diseases. They emphasized that their cell-combination mediated drug delivery strategy could significantly increase the therapeutic efficacy of checkpoint blockade by exploiting the homing ability of HSCs and activation of platelets in situ for improved delivery of a checkpoint inhibitor