Antitumor Humoral and T Cell Responses by Mucin-1 Conjugates of Bacteriophage Qβ in Wild-type Mice

Abstract

Mucin-1 (MUC1) is one of the top ranked tumor associated antigens. In order to generate effective anti-MUC1 immune responses as potential anticancer vaccines, MUC1 peptides and glycopeptides have been covalently conjugated to bacteriophage Qβ. Immunization of mice with these constructs led to highly potent antibody responses with IgG titers over one million, which are among the highest anti-MUC1 IgG titers reported to date. Furthermore, the high IgG antibody levels persisted for more than six months. The constructs also elicited MUC1 specific cytotoxic T cells, which can selectively kill MUC1 positive tumor cells. The unique abilities of Qβ-MUC1 conjugates to powerfully induce both antibody and cytotoxic T cell immunity targeting tumor cells bode well for future translation of the constructs as anticancer vaccines.

Protective Epitope Discovery and Design of MUC1-based Vaccine for Effective Tumor Protections in Immunotolerant Mice

“…23 Azide-modified MUC1 29–31 were coupled with the alkyne-functionalized Q β 24 promoted by Cu 2+ catalyst and ligand 34 (Scheme 4). The numbers of (glyco)peptides introduced onto each Qβ capsid were determined by mass spectrometry analysis of peak intensities of the modified Qβ conjugates vs those of the unmodified subunits, 13 which were 270 on average for these conjugates (Figures S3-S5). The unreacted alkyne groups on Q β capsids were capped using an excess of 3-azido 1-propanol 38 by a second CuAAC reaction.…”

“…Glycans including Tn, T, and cores 1–4 were attached to various locations of the glycopeptides. In addition, mucin-5 (MUC5) glycopeptides 13 and glycoproteins including fetuin, transferin, mucins from porcine stomach, and bovine submaxillary glands have been immobilized on the array (Figures S13 and S14). The slides were incubated with individual mouse serum.…”

Viral nanoparticles for drug delivery, imaging, immunotherapy, and theranostic applications

“…For example, Qβ has been engineered to present TACAs such as the poorly immunogenic monomeric Tn antigen and the ganglioside antigen GM2 [156,157]. Furthermore, tumor associated MUC1 glycopeptide antigens were conjugated to Qβ, and the obtained Qβ-MUC1 vaccine induced high titers of anti-MUC1 IgG antibodies in both MUC1 transgenic and WT mice, conferring protection against primary and metastatic breast cancers [158][159][160]. Likewise, Huang et al developed CPMV-TACA conjugates, specifically targeting the Tn antigen (GalNAc-α-O-Ser/Thr) [161].…”

P‐LME polymer nanocapsules stimulate naïve macrophages and protect them from oxidative damage during controlled drug release

“…In this system, the crystallinity and surface OH groups of AlO‐OH control the activation of the NLRP3 inflammasome in both human THP‐1 myeloid cells and murine bone marrow‐derived dendritic cells . However, several biopolymer materials have shown the inherent activity of nanomaterials in cellular and humoral immune responses . by virtue of physicochemical properties including size, shape, and surface charge that have an impact on the resulting immunological outcomes .…”