title: V gamma 9 V delta 2 T cell cytotoxicity against tumor cells is enhanced by monoclonal antibody drugs--rituximab and trastuzumab.
abstract: V gamma 9 V delta 2 T cells exert potent cytotoxicity toward various tumor cells and adoptive transfer of V gamma 9 V delta 2 T cells is an attractive proposition for cell based immunotherapy. V gamma 9 V delta 2 T cells expanded in the presence of Zoledronate and IL-2 express CD16 (Fc gamma RIII), which raises the possibility that V gamma 9 V delta 2 T cells could be used in conjunction with tumor targeting monoclonal antibody drugs to increase antitumor cytotoxicity by antibody dependent cellular cytotoxicity (ADCC). Cytotoxic activity against CD20-positive B lineage lymphoma or chronic lymphocytic leukemia (CLL) and HER2-positive breast cancer cells was assessed in the presence of rituximab and trastuzumab, respectively. Cytotoxicity of V gamma 9 V delta 2 T cells against CD20-positive targets was higher when used in combination with rituximab. Similarly, V gamma 9 V delta 2 T cells used in combination with trastuzumab resulted in greater cytotoxicity against HER2-positive cells in comparison with either agent alone and this effect was restricted to the CD16(+)V gamma 9 V delta 2 T cell population. Our results show that CD16(+)V gamma 9 V delta 2 T cells recognize monoclonal antibody coated tumor cells via CD16 and exert ADCC similar to that observed with NK cells, even when target cells are relatively resistant to monoclonal antibodies or V gamma 9 V delta 2 T cells alone. Combination therapy involving ex vivo expanded CD16(+)V gamma 9 V delta 2 T cells and monoclonal antibodies may enhance the clinical outcomes for patients treated with monoclonal antibody therapy.
authors.affiliation: Centre for Immune and Targeted Therapy, University of Queensland, Brisbane, Australia.
authors.forename: Hirotake
authors.initials: H
authors.lastname: Tokuyama
authors.forename: Tomomi
authors.initials: T
authors.lastname: Hagi
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Mattarollo
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Morley
authors.forename: Qiao
authors.initials: Q
authors.lastname: Wang
authors.forename: Hang-Fai
authors.initials: HF
authors.lastname: So
authors.forename: Hang
authors.initials: H
authors.lastname: Fai-So
authors.forename: Fuminori
authors.initials: F
authors.lastname: Moriyasu
authors.forename: Mie
authors.initials: M
authors.lastname: Nieda
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Nicol
mesh_terms: D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D061067:Antibodies, Monoclonal, Humanized; D058846:Antibodies, Monoclonal, Murine-Derived; D000920:Antibody-Dependent Cell Cytotoxicity; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000276:immunology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D018925:Chemokines / Q000378:metabolism; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology*; D016393:Lymphoma, B-Cell / Q000188:drug therapy* / Q000276:immunology; D054353:Perforin / Q000378:metabolism; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000032:analysis*; D017452:Receptors, IgG / Q000276:immunology; D000069283:Rituximab; D013601:T-Lymphocytes / Q000276:immunology; D000068878:Trastuzumab; D020298:U937 Cells
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D058846:Antibodies, Monoclonal, Murine-Derived; D000970:Antineoplastic Agents; D018925:Chemokines; D007371:Interferon-gamma; D054353:Perforin; D018719:Erb-b2 Receptor Tyrosine Kinases; D016692:Receptors, Antigen, T-Cell, gamma-delta; D017452:Receptors, IgG; D000069283:Rituximab; D000068878:Trastuzumab