VLPs Improve Treatment for Acute Myeloid Leukemia

Abnormal proliferation of myeloid progenitor cells in the bone marrow, peripheral blood, or extramedullary tissues leads to Acute Myeloid Leukemia (AML), a common form of leukemia in adults, with poor prognosis in elderly patients.

Researchers from the University of Munich and the German Cancer Research Center published a Clinical and Experimental Medicine study, discovering that high SAMHD1 (Sterile alpha motif and histidine‐aspartic acid domain‐containing protein 1) expression is associated with resistance to Ara-C (Arabinofuranosyl Cytidine). The novel Vpx (Viral Protein X) VLPs (virus-like particles) they designed can effectively degrade SAMHD1, enhancing the efficacy of Ara-C, particularly in AML cell lines, providing a new strategy for AML treatment.

AML and SAMHD1

AML is caused by clonal proliferation of myeloid progenitor cells in the bone marrow, peripheral blood, or extramedullary tissues, exhibiting high heterogeneity. Elderly patients often have poor responses and survival rates. SAMHD1, a host restriction factor, degrades nucleotides required for viral replication and is associated with Ara-C resistance in AML patients.

Characteristics of SIV (Simian Immunodeficiency Virus)-Based VLPs

Researchers designed minimized second-generation VLPs devoid of accessory and regulatory proteins, optimizing their yield and packaging efficiency. Specific Vpx/Vpr effectively degrades SAMHD1, and the addition of HIV-1 Rev significantly enhances VLP production.

Function of Second-Generation VLPs in AML Cell Lines

Second-generation VLPs are comparable to first-generation VLPs in degrading SAMHD1 and enhancing Ara-C cytotoxicity, with no cytotoxicity themselves. In AML cell lines with high SAMHD1 expression, second-generation VLPs significantly improve the efficacy of Ara-C.

Differences Between First- and Second-Generation VLPs

Functional differences between second-generation and first-generation VLPs are mainly due to mutations in specific amino acids. The addition of a 3xFLAG tag does not affect Vpx function. By adjusting the amino acid sequence, Vpx function can be restored.

Function of Second-Generation VLPs in Primary AML

In primary AML cells, the efficiency of second-generation VLPs decreases, potentially related to lower VSV-G transduction efficiency. Viral fusion assays show lower virus entry rates in primary AML cells, explaining the poorer effect.

Conclusion

This study successfully designed simplified second-generation VLPs that efficiently degrade SAMHD1 and enhance the efficacy of Ara-C. However, their effectiveness is reduced in primary AML cells, necessitating exploration of more effective targeting strategies. Future research should focus on improving the transduction efficiency of VLPs in primary AML cells.

Boasting over a decade of expertise in CDMO, Yaohai stands at the forefront of VLP production, precisely understanding and fulfilling customers' customized needs for VLPs. The company has successfully trialed VLP vaccines in various projects by leveraging microbial expression systems. Yaohai guarantees the effectiveness of its VLP-based therapies tailored for different diseases.

Yaohai Bio-Pharma is also actively seeking institutional or individual global partners and offers the most competitive compensation in the industry. If you have any questions, please feel free to contact us: [email protected]