Placental Cells Significantly Inhibit Cancer Cell Growth in Newly Published Study

According to the peer-reviewed article in the journal Scientific Reports, placenta-derived cells called PLX cells, exhibit a strong inhibitory effect on various lines of breast, colorectal, kidney, liver, lung, muscle and skin cancers. The research was conducted over more than two years by Pluristem Therapeutics, Inc., a Haifa-based biotechnology company.

The article titled “Human Placental-Derived Adherent Stromal Cells Co-Induced with TNF‑a and IFN‑g Inhibit Triple-Negative Breast Cancer in Nude Mouse Xenograft Models” is based on studies which examined the effect of Pluristem Therapeutic‘s PLX cells that had been induced with tumor necrosis factor alpha (TNF-a) and interferon-gamma (IFN-g), on the proliferation of over 50 lines of human cancerous cells. The induction of the cells was carried out by adjusting their manufacturing process in order to transiently alter their secretion profile.

Data from the first study showed that the modified PLX cells exhibited an anti-proliferative effect on 45% of the tested cancer cell lines, with a strong inhibitory effect on various lines of breast, colorectal, kidney, liver, lung, muscle and skin cancers. Comprehensive bioinformatics analysis identified common characteristics of the cancer cell lines inhibited by PLX cells. This knowledge could potentially be used in the future for screening patients’ tumors to identify those patients most likely to show a positive response to treatment with PLX cells.

Based on these promising results, Pluristem conducted a pre-clinical study of female mice harboring human triple negative breast cancer (TNBC). TNBC is an aggressive form of breast cancer that does not respond to standard hormonal therapy due to a lack of estrogen and progesterone receptors. Current treatment for TNBC consists of a combination of surgery, radiation therapy, and chemotherapy, and yet the prognosis remains poor for patients with this type of breast cancer. In this study, weekly intramuscular (IM) injections of the induced PLX cells produced a statistically significant reduction (p= 0.025) in mean tumor size in the treated group compared with the untreated group, with 30% of the treated mice exhibiting complete tumor remission. In addition, a statistically significant reduction (p=0.003) was seen in the percentage of proliferating tumor cells as well as in the level of blood vessels within the tumors.

“The findings of this study published in a peer-reviewed journal are the outcome of over two years of research as well as the vast knowledge of PLX cell properties we have developed over the last 10 years. We believe the findings show promise for the utilization of our induced PLX cells in slowing and reversing the growth of cancer cells, particularly for some cancers that don’t have viable treatment options,” stated Zami Aberman, Chairman and Co-CEO of Pluristem. “The findings also confirm the effectiveness of IM administration and support a mechanism of action involving immunomodulation and inhibition of angiogenesis and cell proliferation in cancerous conditions. Our unique patented manufacturing platform allows us to alter our cells’ secretion profile in correlation with the targeted cancer cells, which may open new possibilities in the field of oncology to treat solid tumors and may also offer new paths to help millions of patients around the world. As in immunotherapy technology, PLX cells potentially have the ability to communicate with the body and to secrete biological components that enhance regeneration processes and support the body in fighting cancer cells.”

Pluristem has filed patent applications relating to the technology for the induction of PLX cells and the use of these cells for the treatment of cancer.

Study Identifies Subtype of Triple Negative Breast Cancer That Responds Better to Chemotherapy

Researchers at Yale Cancer Center have identified a new subtype of triple negative breast cancer that shows significantly improved response to chemotherapy. Patients with the newly defined “BRCA deficient” subtype experienced better survival with chemotherapy. The study was published on Dec. 13 in PLOS Medicine.

Triple negative breast cancer (TNBC) disproportionately affects younger women and women of African ancestry, contributing to health disparities. In the era of personalized cancer therapy, patients with TNBC remain at considerably higher risk of relapse and death than patients with other breast cancer subtypes, due to the aggressive nature of TNBC and the lack of newer targeted therapies for the disease.

The Yale-led study performed whole exome sequencing ¬— a technique for sequencing all the expressed genes in a genome ¬— on TNBC tumors to identify mutations in specific genes or pathways that may indicate response or resistance to the standard of care, which is anthracycline/taxane (ACT) chemotherapy. Researchers found that tumors carrying mutations in the AR and FOXA1 pathways had a significantly higher response rate, 94.1% compared to 16.6% in tumors without the mutations.

Analysis of genomic, epigenetic, and RNA sequencing data revealed that the combinations of mutations that lowered the levels of functioning BRCA1 and BRCA2 RNA — genes that produce the breast cancer tumor suppressor proteins — were associated with significantly better survival outcomes.

“Low levels of functional BRCA are associated with a greater number of clonal mutations and enhanced immune recruitment, which may explain the greater chemosensitivity of these tumors and better outcomes for patients,” explained Christos Hatzis, assistant professor of medicine and director of Breast Bioinformatics, Yale Cancer Center and senior author on the paper.

“The strong connection of ACT chemosensitivity and immune activity in the newly defined BRCA-deficient phenotype of TNBC could help inform future therapeutic strategies for our patients,” said Lajos Pusztai, M.D., professor of medicine (medical oncology), Yale Cancer Center, and disease aligned research team leader for the Breast Center at Smilow Cancer Hospital.

Additional Yale study authors include Tingting Jiang, Weiwei Shi, Vikram Wali, Charles Li, and Richard Lifton.

The study was funded with grant support from the Breast Cancer Research Foundation.