Pharma Focus Europe

LIXTE Biotechnology and the Netherlands Cancer Institute Unveil Novel Mechanism for LB-100, Enhancing Immunotherapy and Chemotherapy Effectiveness in Preclinical Results

Tuesday, July 18, 2023

LIXTE Biotechnology Holdings, Inc. ("LIXTE" or the "Company") has made a significant breakthrough in cancer research through a fruitful collaboration with the Netherlands Cancer Institute. According to a recent article published in BioRxiv, the joint effort has yielded exciting findings about LIXTE's lead clinical compound, LB-100, and its impact on colon cancer cells.

The study reveals that inhibiting PP2A (a specific protein) in colon cancer cells using LB-100 induces remarkable changes in mRNA processing within these cells. As a result, cancer cells are predicted to produce abnormal proteins, which can be recognized by the immune system. This novel mechanism effectively transforms "cold" tumors, which are unresponsive to the immune system, into "hot" tumors that can be targeted effectively. This discovery adds to the growing evidence of LB-100's ability to enhance cancer cells' sensitivity to immune checkpoint blockade, an important type of immunotherapy.

Dr. John S. Kovach, the CEO and Founder of LIXTE, emphasizes that the combination of LB-100 with immunotherapy is well-supported by extensive pre-clinical data. The new mechanistic understanding strengthens the Company's commitment to developing LB-100 in combination with checkpoint blockade antibodies, raising hopes that ongoing and upcoming clinical trials will yield positive results in cancer treatment.

The research findings also indicate that LB-100 disrupts proper mRNA maturation in cancer cells, leading to a reduced ability of these cells to handle DNA damage. This aligns with previous pre-clinical studies demonstrating the synergistic effects of LB-100 with radiotherapy and various chemotherapies in different cancer models.

The article, titled "PP2A Inhibition Instructs Spliceosome Phosphorylation to Create Splicing Vulnerability in Colon Adenocarcinoma," was authored by Dias et al. from the Netherlands Cancer Institute. The collaboration with a team of scientists headed by Prof. René Bernards, a member of the LIXTE Board of Directors and an expert in Molecular Carcinogenesis, has been highly productive.

Prof. Bernards highlights the scientific evidence supporting the idea that incorrectly spliced mRNAs in cells treated with LB-100 generate neo-antigens, making cancer cells more susceptible to immunotherapies. While other companies are exploring drugs targeting mRNA splicing for this purpose, none have reached the clinical stage. The potency of LB-100 in impacting mRNA splicing further validates its potential in combination with immunotherapy.

This groundbreaking research opens up new possibilities for cancer treatment and holds promise for the development of effective therapeutic approaches in the fight against this devastating disease.

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