title: Anti-MUC1 nanobody can redirect T-body cytotoxic effector function.
abstract: Chimeric antigen T cell receptors provide a good approach for adoptive immunotherapy of cancer, especially in the context of cancerous cells that fail to express major histocompatibility complex antigen and co-stimulatory molecules. Clinical applications of these receptors are limited, mostly due to the xenogenic origin of the antibodies, which cause immunogenic reactions. Nanobodies are the smallest fragments of antibodies that have great homology to human VH and low immunogenic potential. MUC1 is a highly attractive immunotherapeutic target owing to increased expression, altered glycosylation, and loss of polarity in more than 80% of human malignancies. We used anti-MUC1 nanobody as an antigen binding domain, CD28 and CD3zeta as signaling domains, and IgG3 as a spacer in a chimeric receptor construct. This construct was transfected to Jurkat cells. The transfected Jurkat cells were exposed to MUC1-positive MCF7 cells. Then we analyzed the secretion of IL2, proliferation of Jurkat cells, and death of MCF7 cells. These data revealed that the nanobody chimeric receptor can target tumor-associated antigen-positive cells. Regarding the efficient and specific function of nanobody chimeric receptor and non-immunogenic nature of nanobodies, these chimeric receptors might be used as promising candidates for clinical applications.
authors.affiliation: Department of Medical Biotechnology, School of Medical Sciences, Tarbiat Modares University, Tehran, IR Iran.
authors.forename: Seyed Hamid Aghaee
authors.initials: SH
authors.lastname: Bakhtiari
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Rahbarizadeh
authors.forename: Sadegh
authors.initials: S
authors.lastname: Hasannia
authors.forename: Davoud
authors.initials: D
authors.lastname: Ahmadvand
authors.forename: Farnoush Jafari
authors.initials: FJ
authors.lastname: Iri-Sofla
authors.forename: Mohammad Javad
authors.initials: MJ
authors.lastname: Rasaee
mesh_terms: D000906:Antibodies / Q000276:immunology*; D017209:Apoptosis / Q000276:immunology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D017931:DNA Primers / Q000235:genetics; D005822:Genetic Vectors; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D018396:Mucin-1 / Q000276:immunology*; D053758:Nanoparticles; D009369:Neoplasms / Q000276:immunology / Q000628:therapy*; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection
chemical_list: D000906:Antibodies; D017931:DNA Primers; C060192:MUC1 protein, human; D018396:Mucin-1; D011948:Receptors, Antigen, T-Cell; D011993:Recombinant Fusion Proteins