Antitumor activity and carrier properties of novel hemocyanins coupled to a mimotope of GD2 ganglioside

• Published in: European journal of medicinal chemistry 2018-04, Vol.150, p.74-86
• Main Authors: Palacios, Miriam, Tampe, Ricardo, Del Campo, Miguel, Zhong, Ta-Ying, López, Mercedes N., Salazar-Onfray, Flavio, Becker, María Inés
• Format: Article
• Language: English
• Subjects: Antitumor activity; Carrier proteins; GD2 mimotope; Immunogenicity; Melanoma; Mollusk hemocyanins; Sulfo-SMCC crosslinker
• ISSN: 0223-5234; 1768-3254
• DOI: 10.1016/j.ejmech.2018.02.082

Conjugation to carrier proteins is a way to improve the immunogenicity of peptides. Such is the case for peptides mimicking carbohydrate tumor-associated antigens in cancer vaccine development. The most used protein for this purpose is the keyhole limpet hemocyanin (KLH) from Megathura crenulata. Its limited bioavailability has prompted interest in finding new candidates; nevertheless, it is not known whether other hemocyanins might be equally efficient as carrier of carbohydrate peptide mimotopes to promotes anti-tumor responses. Here, we evaluated the carrier and antitumor activity of novel hemocyanins with documented immunogenicity obtained from Concholepas concholepas (CCH) and Fissurella latimarginata (FLH), coupled through sulfo-SMCC to P10, a mimetic peptide of GD2, the major ganglioside constituent of neuroectodermal tumors, and incorporating AddaVax as an adjuvant. The humoral immune responses of mice showed that CCH-P10 and FLH-P10 conjugates elicited specific IgM and IgG antibodies against P10 mimotope, similar to those obtained with KLH-P10, which was used as a positive control. The CCH-P10 and FLH-P10 antisera, exhibited cross-reactivity with murine and human melanoma cells, like anti-CCH and anti-FLH sera suggesting a cross-reaction of CCH and FLH glycosylations with carbohydrate epitopes on the tumor cell surfaces, similar to the KLH antisera. When mice were primed with each hemocyanin-P10 and challenged with melanoma cells, better antitumor effects were observed for FLH-P10 than for CCH-P10 and, as for KLH-P10, irrespective of conjugation. These data demonstrate that CCH and FLH are useful carriers of carbohydrate mimotopes; however, the best antitumor activity of FLH preparations, indicate that is a suitable candidate for further cancer vaccines research. [Display omitted] •P10 peptide a mimotope of GD2 ganglioside was efficiently coupled to CCH and FLH.•CCH and FLH induces high titers of specific IgG antibodies against P10.•CCH and FLH are safe and useful carriers for carbohydrate mimotopes, like to KLH.•Anti P-10 sera shown reactivity against mice and human melanoma cells.•FLH conjugates exhibit the best antitumor effect in a melanoma model, like to KLH.