Wu, XinqiGiobbie-Hurder, AnitaConnolly, Erin M.Li, JingjingLiao, XiaoyunSevergnini, MarianoZhou, JunRodig, ScottHodi, F. Stephen2018-07-252018Wu, Xinqi, Anita Giobbie-Hurder, Erin M. Connolly, Jingjing Li, Xiaoyun Liao, Mariano Severgnini, Jun Zhou, Scott Rodig, and F. Stephen Hodi. 2018. “Anti-CTLA-4 based therapy elicits humoral immunity to galectin-3 in patients with metastatic melanoma.” Oncoimmunology 7 (7): e1440930. doi:10.1080/2162402X.2018.1440930. http://dx.doi.org/10.1080/2162402X.2018.1440930.http://nrs.harvard.edu/urn-3:HUL.InstRepos:37298356ABSTRACT The combination of CTLA-4 blockade ipilimumab (Ipi) with VEGF-A blocking antibody bevacizumab (Bev) has demonstrated favorable clinical outcomes in patients with advanced melanoma. Galectin-3 (Gal-3) plays a prominent role in tumor growth, metastasis, angiogenesis, and immune evasion. Here we report that Ipi plus Bev (Ipi-Bev) therapy increased Gal-3 antibody titers by 50% or more in approximately one third of treated patients. Antibody responses to Gal-3 were associated with higher complete and partial responses and better overall survival. Ipi alone also elicited antibody responses to Gal-3 at a frequency comparable to the Ipi-Bev combination. However, an association of elicited antibody responses to Gal-3 with clinical outcomes was not observed in Ipi alone treated patients. In contrast to being neutralized in Ipi-Bev treated patients, circulating VEGF-A increased by 100% or more in a subset of patients after Ipi treatment, with most having progressive disease. Among the Ipi treated patients with therapy-induced Gal-3 antibody increases, circulating VEGF-A was increased in 3 of 6 nonresponders but in none of 4 responders as a result of treatment. Gal-3 antibody responses occurred significantly less frequently (3.2%) in a cohort of patients receiving PD-1 blockade where high pre-treatment serum Gal-3 was associated with reduced OS and response rates. Our findings suggest that anti-CTLA-4 elicited humoral immune responses to Gal-3 in melanoma patients which may contribute to the antitumor effect in the presence of an anti-VEGF-A combination. Furthermore, pre-treatment circulating Gal-3 may potentially have prognostic and predictive value for immune checkpoint therapy.en-USantibody responses to galectin-3anti-VEGFimmune therapygalectin-3melanomaJournal Article2018-07-2510.1080/2162402X.2018.1440930