0000000000774438
AUTHOR
Adrian Hayday
In vivo manipulation of Vgamma9Vdelta2 T cells with zoledronate and low-dose interleukin-2 for immunotherapy of advanced breast cancer patients.
The potent anti-tumour activities of gamma delta T cells have prompted the development of protocols in which gamma delta-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 V gamma 9V delta 2 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 V gamma 9V delta 2 T …
Immunosurveillance by gamma delta T cells - lessons from the cancer field
The most common contemporary depiction of the immune response is an early innate response, mounted by myeloid cells, followed by a delayed adaptive lymphoid responses mounted by lymphocytes. This depiction is based on myriad compelling data sets and has made powerful predictions with biological and clinical relevance. Nonetheless, it seems incomplete. Thus, there are lymphocytes that respond very rapidly, commonly to self-encoded molecules over-expressed by dysregulated and/or transformed tissues and cells. The evidence for such “lymphoid stress-surveillance” by gamma delta T cells has been provided by animal models, and supports ongoing clinical investigations of the potential host-protect…
Targeting human {gamma}delta} T cells with zoledronate and interleukin-2 for immunotherapy of hormone-refractory prostate cancer.
Abstract The increasing evidence that γδ T cells have potent antitumor activity suggests their value in immunotherapy, particularly in areas of unmet need such as metastatic carcinoma. To this end, we initiated a phase I clinical trial in metastatic hormone-refractory prostate cancer to examine the feasibility and consequences of using the γδ T-cell agonist zoledronate, either alone or in combination with low-dose interleukin 2 (IL-2), to activate peripheral blood γδ cells. Nine patients were enlisted to each arm. Neither treatment showed appreciable toxicity. Most patients were treated with zoledronate + IL-2, but conversely only two treated with zoledronate displayed a significant long-te…