Scientists eliminate cancer stem cells freely in mouse models of myeloproliferation and myeloproliferation-induced senescence

For patients with lymphomas and myelodysplastic syndromes, early-stage natural history immunotherapy such as immunotherapy can efficiently overcome resistance to treatment and make the disease go away. But in several of these patients, unopposed normal, dysregulated gene expression may contribute to the initiation of myelodysplastic syndromes (MDS) or myeloproliferation-induced aberrations.

A recent Tel Aviv University study, published in the journal Nature Communications, solves this longstanding problem: Researchers eliminated cancer stem cells freely in mouse models of myeloproliferation and myeloproliferation-induced senescence and then transplanted them back into these patients. The treatment resulted in severe disease regression in these patients, but left untreated some of the patients unable to drive normal blood formation and eliminate abnormal blood vessels.

“This is not a problem with the disease, but a priority in the cancer field, ” says principal investigator Prof. Yuval Nir of TAU’s Sackler School of Medicine. “Now we’re exploring mechanisms involved in removing cancer cells from the patients, using immunotherapy. This could boost the effectiveness of the mixed-drug immunotherapy already used to treat patients with leukemia, lymphorectal or cervical cancer. “.

Immune checkpoint therapy has revolutionized treatment for cancer patients by significantly shrinking tumor size and allowing them to control their immune attack. Since the onset of myelodysplastic syndromes (MDS) in 2008, there has been a surge in interest in the field. IDS has created a highly motivated and patient-oriented population, fueled by promising clinical results and promising technology. However, current trials of therapies used to treat MDS are not designed to eliminate or even eliminate individual cases of low myeloid-stimulated myeloid-epithelial dysplasia (MSID—for short, malignant brain tumors caused by myeloid-derived suppressor genes). Rather, they aim to improve disease outcomes for the most active patients.

Currently available therapies for MSIDs include myelosuppressive drugs or cytotoxic immune checkpoint blockade therapy, but these are not standard treatments for MDS. The academic laboratory of Dr. Nir and Dr. Selau, in collaboration with Dr. Nir, had previously developed a technology-enhanced immuno-therapy vaccine (TXP) that combines TXP and myelosuppressive drugs. The TXP vaccine induces myelosuppressive activity in genetically engineered mice and mice engineered with normal human MDS genes. The new immuno-therapy approach includes eliminating cancer cells and enhancing the normal formation of blood vessels by the re-segregating of myeloid blood vessels, which significantly enhances the survival of the treated mice.

“The first step had been to create an immuno-therapy vaccine, ” says Prof. Nir, who is also professor of molecular and cell biology at TAU’s Sackler School of Medicine. “In the absence of standard therapies, immuno-therapy using TXP and myelosuppressive drugs reduced the size of the infiltrating immune cells and placental blood vessels, and improved the functions of normal blood-vesicle barrier function. “

Immunogen therapy provokes the production of proteins, which cause myeloid cells to secrete extracellular matrix, which helps blood vessels relax and provide a protective barrier against infections. In ACA immuno-armored T cells, the protein CR1 was targeted, leading to permanent activation of the regulatory T cells and extracellular matrix as well as stimulation of gene expression.

Through the inhibition of CR1, the myeloid cells appeared to strengthen their internal and external walled blood vessels and become less permeable to harmful radiation and microvesicles. Enhanced blood vessel integrity was also observed in animal models engineered to express CR1 in ACA-deficient mouse cells. In the study, mice treated with CR1 showed superiority to control animals treated with standard therapies.