Clinical evaluation of autologous gamma delta T cell-based immunotherapy for metastatic solid tumours

• Published in: British journal of cancer Vol. 105; no. 6; pp. 778 - 786
• Main Authors: Nicol, A J, Tokuyama, H, Mattarollo, S R, Hagi, T, Suzuki, K, Yokokawa, K, Nieda, M
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 06.09.2011; Nature Publishing Group
• Subjects: 639/638/92/436/108; 692/699/67; 692/700/565/251; 692/700/565/809; Adoptive transfer; Aged; Antibody-dependent cell-mediated cytotoxicity; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Cancer; Cancer Research; Cell migration; Chemokine receptors; Clinical Study; Cytotoxicity; Diphosphonates - administration & dosage; Drug Resistance; Epidemiology; Feasibility Studies; Female; Humans; Imidazoles - administration & dosage; Immunotherapy; Immunotherapy, Adoptive - adverse effects; Immunotherapy, Adoptive - methods; Liver; Lung; Lymphocyte Activation - immunology; Lymphocytes T; Male; Medical sciences; Memory cells; Metastases; Middle Aged; Molecular Medicine; Multiple tumors. Solid tumors. Tumors in childhood (general aspects); Neoplasm Metastasis; Neoplasms - pathology; Neoplasms - therapy; Oncology; Receptors, Antigen, T-Cell, gamma-delta - metabolism; Spleen; T-Lymphocyte Subsets - immunology; T-Lymphocytes - immunology; Toxicity; Treatment Outcome; Tumors; Zoledronic acid; clinical trial; 2 T cells; 9V; V; gamma delta T cells; immunotherapy; Solid tumor; γ/δ T cell receptor; Vγ9Vδ2 T cells; Malignant tumor; Metastasis; Cell immunotherapy; Cancerology; Treatment; T-Lymphocyte; Clinical trial; Advanced stage; Cancer
• ISSN: 0007-0920; 1532-1827; 1532-1827
• DOI: 10.1038/bjc.2011.293

Background: Adoptive transfer of ex vivo expanded autologous V γ 9V δ 2 T cells may be of therapeutic benefit for cancer because of their potent direct cytotoxicity towards tumour cells, synergistic cytotoxicity when combined with aminobisphosphonates and enhancement of antibody-dependent cell-mediated cytotoxicity. Methods: To determine the feasibility and clinical safety of therapy with ex vivo expanded, activated V γ 9V δ 2 T cells in combination with zoledronate, we enrolled 18 subjects with advanced solid tumours into a phase I clinical study. Administered indium 111 -oxine-labelled V γ 9V δ 2 T cells were tracked in a cohort of patients. Results: Administered V γ 9V δ 2 T cells had an activated effector memory phenotype, expressed chemokine receptors predictive of homing to peripheral tissues and were cytotoxic in vitro against tumour targets. Adoptively transferred V γ 9V δ 2 T cells trafficked predominantly to the lungs, liver and spleen and, in some patients, to metastatic tumour sites outside these organs. No dose-limiting toxicity was observed, but most patients progressed on study therapy. However, three patients administered V γ 9V δ 2 T cells while continuing previously ineffective therapy had disease responses, suggesting an additive effect. Conclusion: Therapy with aminobisphosphonate-activated V γ 9V δ 2 T cells is feasible and well tolerated, but therapeutic benefits appear only likely when used in combination with other therapies.