Microbiome cure for cancer?
10月
8日
See report, https://www.aacr.org/Meetings/Pages/MeetingDetail.aspx?EventItemID=101
Treating Lymphoma & Melanoma with mRNA
The vaccine potential of mRNA lipid nanoparticles was evaluated by performing studies after delivery in mice. The preclinical antitumor efficacy was assessed in a lymphoma (EG7-OVA) and melanoma (B16-OVA ) model. In addition to evaluating overall survival, experiments were performed where tumors were isolated after immunization and screened for effector responses (e.g., antigen-specific CD8+ T-cells and NK cells) and suppressive mechanisms that could impact the positive outcome.
To tackle adaptive resistance to activated T-cells, the study evaluated a combinatory therapy of the mRNA vaccine with anti-PDL1 antibodies (8). Upon injection in mice, these particles are mainly detected within APCs (macrophages and dendritic cells) in lungs and spleen. This resulted in high mRNA expression as well as functional activation of the particle-loaded immune cells, marked by cytokine production of IL-12p70 and IFN-γ. The study was able to optimize combinations of therapeutic nanoparticles with modified mRNA, which resulted in 6 to 7 times higher numbers of tumor-infiltrating antigen-specific T-cells compared to unmodified mRNA particles. This resulted in a 2- to 3-fold increase in intratumoral NK cells, compared to untreated mice.
These mice exhibited reduced immune suppression at the tumor site. It resulted in clear synergistic antitumor effects between the mRNA nanoparticles and anti-PDL1 checkpoint blocking antibodies.
The study developed a flexible and versatile mRNA nanoparticle platform that effectively initiates immunity by targeting and activating immune cells!. Combining immune-silent mRNA with immune-therapy evokes a safe effective immune response.
See '"Abstract B136: Optimized messenger RNA immunolipoplexes for cancer immunotherapy: Balancing immunogenicity and adjuvancy", by
Rein Verbeke, Ine Lentacker, Karine Breckpot, Serge Van Calenbergh, Stefaan C. De Smedt and Heleen Dewitte, February 2019; https://cancerimmunolres.aacrjournals.org/content/7/2_Supplement/B136.abstract
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