Details

Autor(en) / Beteiligte

• Lang, Joshua M
• Kaikobad, Mahazarin R
• Wallace, Marianne
• Staab, Mary Jane
• Horvath, Dorothea L
• Wilding, George
• Liu, Glenn
• Eickhoff, Jens C
• McNeel, Douglas G
• Malkovsky, Miroslav

Titel

Pilot trial of interleukin-2 and zoledronic acid to augment gamma delta T cells as treatment for patients with refractory renal cell carcinoma

Ist Teil von

• Cancer Immunology, Immunotherapy, 2011-10, Vol.60 (10), p.1447-1460

Erscheinungsjahr

2011

Link zum Volltext

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• Prior to the advent of VEGF-targeted therapies, renal cell carcinoma (RCC) was among the few solid tumors shown to respond to cytokine-based therapies such as interleukin-2 (IL-2) and interferon alpha. Previous work has shown that aminobisphosphonates, including zoledronic acid (ZA), are capable of activating human V gamma 9 V delta 2 T cells in vitro, and these cells can be further expanded with IL-2. Moreover, these V gamma 9 V delta 2 T cells have cytolytic activity in vitro to multiple human tumor cell lines. In the current report, we have conducted a pilot trial in patients with metastatic RCC, evaluating different doses of ZA in combination with low-dose IL-2 to determine whether combining these agents can promote in vivo proliferation of V gamma 9 V delta 2 T cells and elicit an antitumor response. In 12 patients evaluated, no objective clinical responses were observed by RECIST criteria; however, two patients experienced prolonged stable disease. A modest increase in V gamma 9 V delta 2 T-cell frequency could be detected by Day 8 of therapy in four of the nine patients who received at least one cycle of therapy, but not to the magnitude anticipated from preclinical models. Repeated administration of IL-2 and ZA resulted in both a diminished in vivo percentage of V gamma 9 V delta 2 T cells as well as impaired expansion in vitro after the first cycle of therapy. These results suggest that repeated administration of IL-2 and ZA, at the doses and schedules used in this trial, may actually inhibit the proliferative capacity of V gamma 9 V delta 2 T cell in patients with metastatic RCC.