title: Microencapsulation of therapeutic bispecific antibodies producing cells: immunotherapeutic organoids for cancer management.
abstract: Regardless of the important therapeutic advances developed over the last years for the management of cancer, the fact is that many patients still suffer from a tremendous reduction on their quality of life due to lack of complete selectivity of conventionally administered chemotherapeutic drugs. In the search of more efficacious tumor-targeted therapies, the use of bispecific antibodies (bsAbs) capable of simultaneous binding to tumor-associated antigens and to an activating receptor, such as CD3, has emerged as a promising approach. With the intention to complementing and improving this cancer immunotherapy, human HEK-293 cells have been genetically modified ex vivo to secrete a recombinant anti-CEA (carcinoembryonic antigen) × anti-CD3 bsAb. After encapsulation in alginate-poly-l-lysine microcapsules, bsAb-secreting HEK-293 cells were monitorized for several weeks. This system has proved to be feasible for the maintenance of cell growth and recombinant antibody production giving proof-of-concept of its use as immunotherapeutic organoids in cancer treatment.
authors.affiliation: NanoBioCel Group, Laboratory of Pharmaceutics, School of Pharmacy, University of the Basque Country UPV/EHU , Vitoria-Gasteiz , Spain .
authors.forename: Laura
authors.initials: L
authors.lastname: Saenz del Burgo
authors.forename: Marta
authors.initials: M
authors.lastname: Compte
authors.forename: Mónica
authors.initials: M
authors.lastname: Aceves
authors.forename: Rosa María
authors.initials: RM
authors.lastname: Hernández
authors.forename: Laura
authors.initials: L
authors.lastname: Sanz
authors.forename: Luis
authors.initials: L
authors.lastname: Álvarez-Vallina
authors.forename: Jose Luis
authors.initials: JL
authors.lastname: Pedraz
mesh_terms: D000464:Alginates / Q000737:chemistry*; D018033:Antibodies, Bispecific / Q000008:administration & dosage / Q000276:immunology / Q000627:therapeutic use*; D000951:Antigens, Neoplasm / Q000276:immunology; D001666:Binding Sites, Antibody; D017252:CD3 Complex / Q000276:immunology*; D002272:Carcinoembryonic Antigen / Q000276:immunology*; D004339:Drug Compounding; D005240:Feasibility Studies; D057809:HEK293 Cells; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D009940:Organoids / Q000737:chemistry*; D011107:Polylysine / Q000031:analogs & derivatives* / Q000737:chemistry
chemical_list: D000464:Alginates; D018033:Antibodies, Bispecific; D000951:Antigens, Neoplasm; D017252:CD3 Complex; D002272:Carcinoembryonic Antigen; C051546:alginate-polylysine-alginate; D011107:Polylysine
keywords: Active targeting; alginate; biomaterials; bispecific antibody; cell factories; drug delivery; immunotherapy; nanomedicine