Novel antibody drug class could mean faster arrival of immunotherapies
Nature Medicine reports elimination of large tumors in mice by messenger rna-encoded bispecific antibodies
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MAINZ, Germany—June 12 saw BioNTech AG, a biotechnology company focused on individualized cancer immunotherapy, report preclinical data featuring a novel class of mRNA-encoded antibody drugs called RiboMABs. In Nature Medicine, BioNTech presented the application of this technology for mRNA-based in-vivo delivery of T cell-engaging bispecific antibodies. The study was titled “Elimination of large tumors in mice by mRNA-encoded bispecific antibodies.”
Bispecific antibodies act by connecting human immune cells to tumor cells for highly efficient killing and have demonstrated great promise as immunotherapy agents; however, BioNTech notes, the challenges that go along with demanding procedures—production, purification and formulation of a recombinant protein—hinder the development of new drugs in this class.
Administering the mRNA encoding the bispecific antibody, thus enabling the patient’s body to synthesize the therapeutic protein, may profoundly reduce complexity of drug development.
BioNTech researchers achieved this aim by incorporating modified nucleosides into the pharmacologically optimized mRNA and using liver targeting nanoparticles to ensure prolonged production in vivo. Intravenously injecting a few micrograms of mRNA resulted in bispecific RiboMAB production in the liver cells that rapidly secreted into the circulation, reaching peak level within hours and remaining at therapeutically effective plasma concentrations for a week.
To demonstrate universality of this novel approach, bispecific RiboMABs targeting different tumor antigens were generated, and their therapeutic potency was tested in mice bearing human tumors and repopulated with human immune cells. Weekly application of any of the bispecific RiboMAB, directed against cancer antigens that are present in many human cancers, resulted in elimination of aggressively growing, large tumors. This is reportedly the first preclinical study to demonstrate in-vivo application of mRNA-encoded antibodies for successful treatment of cancer.
“Our data show that with low doses of mRNA encoding a bispecific antibody, we get sustained production of RiboMAB comparable to those of naturally produced immunoglobulin proteins and capable of curing advanced cancers in mice,” said Prof. Ugur Sahin, founder and CEO of BioNTech, who led the study. “What we have learned about RiboMAB pharmacology provides a sound basis for moving towards first clinical testing of this approach in cancer patients.”
BioNTech works the range from diagnostics and drug development to manufacturing. Its cutting-edge technologies range from individualized mRNA-based medicines through innovative chimeric antigen receptors and T cell receptor-based products to novel checkpoint immunomodulators. Founded in 2008, BioNTech’s financial shareholders include the MIG Fonds, Salvia and the Strüngmann Family Office, with the Strüngmann Family Office as the majority shareholder.
