Mofayezi, A. | Search bioRxiv

bioRxiv2024

Effective targeting of CD19 positive primary B-ALL cells using CAR-NK cells generated with mRNA-LNPs

1.Chimeric antigen receptor natural killer (CAR-NK) cell therapy is recognized as a promising modality for the treatment of hematologic malignancies, particularly B-cell malignancies. In this study, we developed "off-the-shelf" anti-CD19 CAR-NK cells using anti-CD19 CAR mRNAs formulated in proprietary ionizable lipid nanoparticles (LNPs). The efficiency of mRNA-LNP delivery into umbilical cord blood (UCB)-derived NK cells and primary T cells was evaluated in an in-vitro setting, demonstrating superior delivery efficiency in NK cells. Further investigation showed a probable role for an endocytic mechanism, macropinocytosis, in efficient transfection of NK cells with LNPs. Nevertheless, CAR-NK cells generated through this mRNA-LNP platform exhibited significantly enhanced cytotoxicity against CD19+ target cells, such as EGFP+Raji stable cell line and primary malignant B cells derived from refractory/relapsed B-cell acute lymphoblastic leukemia (B-ALL) patients. These findings highlight the promise of the mRNA-LNP platform in advancing CAR-NK therapies against B-cell malignancies.

cancer biology↗

bioRxiv2022

mRNA-based vaccine candidate COReNAPCIN(R) induces robust humoral and cellular immunity in mice and non-human primates

At the forefront of biopharmaceutical industry, the messenger RNA (mRNA) technology offers a flexible and scalable platform to address the urgent need for world-wide immunization in pandemic situations. This strategic powerful platform has recently been used to immunize millions of people proving both of safety and highest level of clinical efficacy against infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here we provide preclinical report of COReNAPCIN(R); a vaccine candidate against SARS-CoV-2 infection. COReNAPCIN(R) is a nucleoside modified mRNA-based vaccine formulated in lipid nanoparticles (LNPs) for encoding the full-length prefusion stabilized SARS-CoV-2 spike glycoprotein on the cell surface. Vaccination of C57BL/6 and BALB/c mice and rhesus macaque with COReNAPCIN(R) induced strong humoral responses with high titers of virus-binding and neutralizing antibodies. Upon vaccination, a robust SARS-CoV-2 specific cellular immunity was also observed in both mice and non-human primate models. Additionally, vaccination protected rhesus macaques from symptomatic SARS-CoV-2 infection and pathological damage to the lung upon challenging the animals with high viral loads of up to 2x108 live viral particles. Overall, our data provide supporting evidence for COReNAPCIN(R) as a potent vaccine candidate against SARS-CoV-2 infection for clinical studies.

immunology↗