TY - JOUR
T1 - In vivo manipulation of V9V2 T cells with zoledronate and low-dose interleukin-2 for immunotherapy of advanced breast cancer patients
AU - Meraviglia, S.
AU - Eberl, M.
AU - Vermijlen, D.
AU - Todaro, M.
AU - Buccheri, S.
AU - Cicero, G.
AU - La Mendola, C.
AU - Guggino, G.
AU - D'Asaro, M.
AU - Orlando, V.
AU - Scarpa, F.
AU - Roberts, A.
AU - Caccamo, N.
AU - Stassi, G.
AU - Dieli, F.
AU - Hayday, A. C.
PY - 2010/8
Y1 - 2010/8
N2 - The potent anti-tumour activities of γδ T cells have prompted the development of protocols in which γδ-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, a Vγ9Vδ2 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 Vγ9Vδ2 T cells in all patients. However, a statistically significant correlation of clinical outcome with peripheral Vγ9Vδ2 T cell numbers emerged, as seven patients who failed to sustain Vγ9Vδ2 T cells showed progressive clinical deterioration, while three patients who sustained robust peripheral Vγ9Vδ2 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 Vγ9Vδ2 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 treatment-refractory patients with advanced breast cancer.
AB - The potent anti-tumour activities of γδ T cells have prompted the development of protocols in which γδ-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, a Vγ9Vδ2 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 Vγ9Vδ2 T cells in all patients. However, a statistically significant correlation of clinical outcome with peripheral Vγ9Vδ2 T cell numbers emerged, as seven patients who failed to sustain Vγ9Vδ2 T cells showed progressive clinical deterioration, while three patients who sustained robust peripheral Vγ9Vδ2 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 Vγ9Vδ2 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 treatment-refractory patients with advanced breast cancer.
KW - cytokines
KW - cytotoxicity
KW - immunotherapy
KW - metastatic breast cancer
KW - Vγ9Vδ2 T cells
UR - http://www.scopus.com/inward/record.url?scp=77954652637&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77954652637&partnerID=8YFLogxK
U2 - 10.1111/j.1365-2249.2010.04167.x
DO - 10.1111/j.1365-2249.2010.04167.x
M3 - Article
C2 - 20491785
AN - SCOPUS:77954652637
VL - 161
SP - 290
EP - 297
JO - Clinical and Experimental Immunology
JF - Clinical and Experimental Immunology
SN - 0009-9104
IS - 2
ER -