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In vivo manipulation of Vgamma9Vdelta2 T cells with zoledronate and low-dose interleukin-2 for immunotherapy of advanced breast cancer patients

Meraviglia, S., Eberl, Matthias, Vermijlen, D., Todaro, M., Buccheri, S., Cicero, G., La Mendola, C., Guggino, G., D'Asaro, M., Orlando, V., Scarpa, F., Roberts, A., Caccamo, N., Stassi, G., Dieli, F. and Hayday, A. C. 2010. In vivo manipulation of Vgamma9Vdelta2 T cells with zoledronate and low-dose interleukin-2 for immunotherapy of advanced breast cancer patients. Clinical and Experimental Immunology 161 (2) , pp. 290-297. 10.1111/j.1365-2249.2010.04167.x

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Abstract

The potent anti-tumour activities of gd T cells have prompted the development of protocols in which gd-agonists are administered to cancer patients. Encouraging results from small Phase I trials have fuelled efforts to characterize more clearly the application of this approach to unmet clinical needs such as metastatic carcinoma. To examine this approach in breast cancer, a Phase I trial was conducted in which zoledronate, aVg9Vd2 T cell agonist, plus low-dose interleukin (IL)-2 were administered to 10 therapeutically terminal, advanced metastatic breast cancer patients. Treatment was well tolerated and promoted the effector maturation of Vg9Vd2 T cells in all patients. However, a statistically significant correlation of clinical outcome with peripheral Vg9Vd2 T cell numbers emerged, as seven patients who failed to sustain Vg9Vd2 T cells showed progressive clinical deterioration, while three patients who sustained robust peripheral Vg9Vd2 cell populations showed declining CA15-3 levels and displayed one instance of partial remission and two of stable disease, respectively. In the context of an earlier trial in prostate cancer, these data emphasize the strong linkage of Vg9Vd2 T cell status to reduced carcinoma progression, and suggest that zoledronate plus low-dose IL-2 offers a novel, safe and feasible approach to enhance this in a subset of treatmentrefractory patients with advanced breast cancer.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Systems Immunity Research Institute (SIURI)
Subjects: Q Science > QR Microbiology > QR180 Immunology
R Medicine > R Medicine (General)
Uncontrolled Keywords: cytokines, cytotoxicity, immunotherapy, metastatic breast cancer,Vg9Vd2 T cells
Publisher: Wiley-Blackwell
ISSN: 0009-9104
Last Modified: 11 Sep 2020 08:39
URI: http://orca.cf.ac.uk/id/eprint/26362

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