title: Antimalarial activity of granzyme B and its targeted delivery by a granzyme B-single-chain Fv fusion protein.
abstract: We present here the first evidence that granzyme B acts against Plasmodium falciparum (50% inhibitory concentration [IC50], 1,590 nM; 95% confidence interval [95% CI], 1,197 to 2,112 nM). We created a novel antimalarial fusion protein consisting of granzyme B fused to a merozoite surface protein 4 (MSP4)-specific single-chain Fv protein (scFv), which targets the enzyme to infected erythrocytes, with up to an 8-fold reduction in the IC50 (176 nM; 95% CI, 154 to 202 nM). This study confirms the therapeutic efficacies of recombinant antibody-mediated antimalarial immunotherapeutics based on granzyme B.
authors.affiliation: Fraunhofer Institute for Molecular Biology and Applied Ecology IME, Department of Pharmaceutical Product Development, Aachen, Germany RWTH Aachen University, Institute for Molecular Biotechnology, Aachen, Germany.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Kapelski
authors.affiliation: Fraunhofer Institute for Molecular Biology and Applied Ecology IME, Department of Pharmaceutical Product Development, Aachen, Germany RWTH Aachen University, Institute for Molecular Biotechnology, Aachen, Germany.
authors.forename: Melanie
authors.initials: M
authors.lastname: de Almeida
authors.affiliation: Fraunhofer Institute for Molecular Biology and Applied Ecology IME, Department of Pharmaceutical Product Development, Aachen, Germany RWTH Aachen University, Institute for Molecular Biotechnology, Aachen, Germany.
authors.forename: Rainer
authors.initials: R
authors.lastname: Fischer
authors.affiliation: Fraunhofer Institute for Molecular Biology and Applied Ecology IME, Department of Pharmaceutical Product Development, Aachen, Germany Institute for Applied Medical Engineering at RWTH Aachen University Hospital, Department of Experimental Medicine and Immunotherapy, Aachen, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Barth
authors.affiliation: Fraunhofer Institute for Molecular Biology and Applied Ecology IME, Department of Pharmaceutical Product Development, Aachen, Germany RWTH Aachen University, Institute for Molecular Biotechnology, Aachen, Germany rolf.fendel@ime.fraunhofer.de.
authors.forename: Rolf
authors.identifier: http://orcid.org/0000-0003-4716-0311
authors.initials: R
authors.lastname: Fendel
mesh_terms: D000953:Antigens, Protozoan / Q000008:administration & dosage; D000962:Antimalarials / Q000008:administration & dosage / Q000494:pharmacology*; D016503:Drug Delivery Systems / Q000379:methods*; D053804:Granzymes / Q000008:administration & dosage / Q000494:pharmacology*; D057809:HEK293 Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D021261:Parasitic Sensitivity Tests; D010963:Plasmodium falciparum / Q000187:drug effects*; D015800:Protozoan Proteins / Q000008:administration & dosage; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000494:pharmacology; D057127:Single-Chain Antibodies / Q000008:administration & dosage
chemical_list: D000953:Antigens, Protozoan; D000962:Antimalarials; D015800:Protozoan Proteins; D011993:Recombinant Fusion Proteins; D057127:Single-Chain Antibodies; C118839:merozoite surface protein 4, Plasmodium; D053804:Granzymes