Technology Platforms

Online inquiry

  • Email:
  • Technology Platforms

    Creative Biolabs employs messenger RNA (mRNA) to unleash and boost the immune response against a tumor or infectious agent. Researches show that this approach results in long-lasting clinical remission in cancer patients and protective immunity against infections. Here we make a brief introduction about two technologies widely used in mRNA research.

    TriMix Technology

    It is widely accepted that boosting immune response through the dendritic cell (DC) pathway is a targeted, safe and sustainable way. TriMix technology comprises three mRNAs encoding proteins that act together to significantly increase immune responses. In detail, TriMix means a mixture of three mRNA molecules encoding for CD40L, caTLR4 and CD70. This technology was successfully applied in a Phase Ia clinical trial to treat advanced melanoma patients. In the circumstance where the tumor-associated antigens are not known or available, scientists usually aimed to test the direct intratumoral injection of TriMix mRNA. Upon this treatment, tumor-resident DCs were shown to specifically engulf and express the mRNA and were reprogrammed to mature and migrate towards the tumor-draining lymph nodes, resulting in the induction of tumor-specific cytotoxic T lymphocytes (CTLs) in different tumor models.

    • TLR4, activating the immune system as it evokes DCs to present antigens to the CD4/CD8 T-cells
    • CD40L, inducing the DCs to initiate the antigen-specific action of the CD4 T-cells
    • CD70, inducing the DCs to initiate the immune system of the CD8 T-cells
    mRNA encoding for TriMix as a tool for intratumoral immunization. Fig.1 mRNA encoding for TriMix as a tool for intratumoral immunization. (Van der Jeught, 2015)

    TriMix cellular products - stand-alone or combined with a checkpoint inhibitor - has demonstrated broad application across major cancer types, both preclinically and clinically, offering the prospect of therapeutic vaccines and localized tumor treatments acting synergistically with standard of care treatments.

    Advantages

    • Providing an additional triple boost
    • Enhancing the activation and maturation of DCs
    • Stimulating the processes that lead to activated helper T-cells
    • Promoting the processes that result in activated cytotoxic T-cells

    LPR Technology

    Currently, mRNA-based vaccines are being developed for treating various diseases including cancers. For this purpose, synthetic or in vitro transcribed (IVT) mRNA encoding tumor antigen offers several advantages over plasmid DNA encoding tumor antigen including better delivery and security. Liposomes/Polymer/mRNA ternary complexes termed lipoplyplexes (LPR) can be used to deliver mRNA encoding antigen in vivo. Studies reported the preparation of mannosylated mRNA nanoparticles (Man-LPR) loaded with mRNA encoding a melanoma antigen MART-1. Immunization with LPR instigated extremely potent T-cell responses and showed superior effectiveness in controlling tumor growth compared to intravenous immunization with antigen mRNA electroporated DCs.

    The illustration of LPR composition. Fig.2 The illustration of LPR composition. (Pichon, 2013)

    Advantages

    • Combining the beneficial properties of lipid-based and polymer-based nanoparticles
    • Lowered cellular toxicities
    • Improved colloidal stabilities

    Reference

    1. Van der Jeught, K.; et al. Targeting the tumor microenvironment to enhance antitumor immune responses. Oncotarget. 2015, 6(3): 1359.
    2. Pichon, C.; Midoux P. Mannosylated and histidylated LPR technology for vaccination with tumor antigen mRNA. Synthetic Messenger RNA and Cell Metabolism Modulation. Humana Press, Totowa, NJ. 2013, 247-274.
    For Research Use Only.