The potential of VISTA to act as an NCR in the setting of cancer was first demonstrated by Wang and colleagues in a murine model of methylcholanthrene 105 (MCA105)–induced fibrosarcoma (56). MCA105 tumor cells engineered to overexpress VISTA-RFP were shown to grow in animals with immunity protective against the growth of control MCA105 cells. More recently, Le Mercier and colleagues described elevated VISTA expression on leukocytes within the TME and tumor-draining lymph nodes in murine cancer models (60). They also examined the use of an anti-VISTA mAb for intervention and found that VISTA blockade impaired tumor growth, with particularly dramatic results when used in combination with a tumor vaccine (60). Within the TME, a shift was generated toward antitumor immunity with elevated infiltration, proliferation, and T-cell effector function.
As compared with the activity of anti-CTLA4, anti-PD1, and anti-PDL1 in preclinical studies, the VISTA blockade data appear compelling (61–63). Similar to the findings of Wang and colleagues (56), Sorensen and colleagues reported melanoma regression and long-term survival rates of 30% to 40% in a study of CTLA4 blockade in combination with CD40 stimulation and the administration of an adenoviral vaccine.
Lines, J. Louise et al. "VISTA Is a Novel Broad-Spectrum Negative Checkpoint Regulator for Cancer Immunotherapy." Cancer immunology research 2.6 (2014): 510–517. PMC. Web. 4 Feb. 2016.
|What is VISTA / B7-H5 / GI24 immune checkpoint||VISTA / B7-H5 / GI24 immune checkpoint pathway|
|VISTA / B7-H5 / GI24 immune checkpoint antibodies||VISTA / B7-H5 / GI24 immune checkpoint proteins|