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Shackled together, stem cells and platelets can help us escape cancer, report UCLA scientists. In the scientists' study, the cancer is leukemia, and the defiant ones include a guide, a hematopoietic stem cell (HSC), and a drug carrier, an engineered platelet. The guide brings the duo to the bone marrow, and the drug carrier delivers the checkpoint inhibition therapy.
In experiments with mice that had acute myeloid leukemia, the UCLA team found that their unusual combination therapy halted the disease from developing any further. Of the mice that received treatment, 87.5 percent were treated by 80 days after the combination cells were injected. Those mice were also resistant to leukemia cells that were re-injected two months after the 80-day period.
Additional details appeared October 29 in the newspaper Nature Biomedical EngineeringConjugation of haematopoietic stem cells and platelets decorated with anti-PD-1 antibodies augments anti-leukemia efficacy. "As the title indicates, the modified platelets have been able to deliver cancer immunotherapy because they are equipped with antibodies against program cell death protein 1 (PD-1), an immune checkpoint protein that studies the surface of cells and guards against autoimmunity. By binding PD-1, checkpoint inhibitor drugs "release the brakes" on T-cell anticancer activity.
Following intravenous injection into mice bearing leukemia cells, the HSC-platelet-aPD-1 conjugate migrated to the bone marrow and localized released aPD-1, significantly enhancing anti-leukemia immune responses, and increasing the number of active cells. cytokines and chemokines, and the survival of the mice, "the articles authors indicated. "This cell conjugate also promotes resistance to re-challenge with leukemia cells."
This unusual immunotherapy approach could be used with other therapies, such as chemotherapy and stem cell treatment, to improve their effectiveness, "noted the study's senior author, Zhen Gu, Ph.D., professor of bioengineering at the UCLA Samueli School of Medicine. Engineering. Dr. Gu added, however, the method would have been tested and approved in human clinical trials before it could be incorporated into treatments for people with leukemia.
Acute myeloid leukemia is a cancer that starts in bone marrow and can spread to the bloodstream and other parts of the body. With a compromised immune system, a person with this type of leukemia could die from complications from other diseases.
As a treatment for leukemia, chemotherapy on its own is only moderately effective: Leukemia fails to go into remission in about 1 in 3 patients following chemotherapy, according to the American Cancer Society. And about half of people with the disease who can experience a relapse – usually within two years after treatment – usually because cancer can not reach cancer cells in bone marrow.
The UCLA-led research aims to solve the problem by devising a method to deliver medicine directly to the bone marrow. The approach, termed "cell combination drug delivery," is the first to link two different cells together for therapeutic purposes.
"This platelet is a delivery truck," Dr. Gu explained. "We can package drugs or immune system boosters on the cell surface of platelets, and have them activated to the target site inside the body."
The HSC part of the cell combination can find its way into the marrow through specific chemical signals. "The hematopoietic stem cells are a homing signal to the bone marrow," Dr. Noany Quanyin, Ph.D., a lead author of the paper and a doctoral student in Dr. Gu's research group. "Once the stem cells guide the cells into the marrow, the platelets can be activated, they release immunotherapy cargoes inside the marrow to facilitate the body's own defenses, in this case T cells, to kill leukemia cells."
The researchers indicated that they plan to continue studying the approach to potential therapy for leukemia and other diseases. They emphasized that by taking advantage of the homing capability of HSCs and in situ Activation of platelets for the enhanced delivery of a checkpoint inhibitor, their combination-mediated drug delivery strategy could significantly increase the therapeutic efficacy of checkpoint blockade.
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