In the development of vaccines for epithelial tumors, the key targets are MUC1 proteins, which have a variable number of tandem repeats (VNTR) bearing tumor-associated carbohydrate antigens (TACAs), such as Tn and STn. A major obstacle in vaccine development is the low immunogenicity of the short MUC1 peptide. To overcome this obstacle, we designed, synthesized, and evaluated several totally synthetic self-adjuvanting vaccine candidates with self-assembly domains. These vaccine candidates aggregated into fibrils and displayed multivalent B-cell epitopes under mild conditions. Glycosylation of Tn antigen on the Thr residue of PDTRP sequence in MUC1 VNTR led to effective immune response. These vaccines elicited a high level antibody response without any adjuvant and induced antibodies that recognized human breast tumor cells. These vaccines appeared to act through a T-cell independent pathway and were associated with the activation of cytotoxic T cells. These fully synthetic, molecularly defined vaccine candidates had several features that hold promise for anticancer therapy.

Multivalent synthetic vaccines were obtained by solid-phase synthesis of tumor-associated MUC1 glycopeptide antigens and their coupling to a Pam3 Cys lipopeptide through click reactions. These vaccines elicited immune responses in mice without the use of any external adjuvant. The vaccine containing four copies of a MUC1 sialyl-TN antigen showed a significant cluster effect. It induced in mice prevailing IgG2a antibodies, which bind to MCF-7 breast tumor cells and initiate the killing of these tumor cells by activation of the complement-dependent cytotoxicity complex.

Immunotherapy is believed to be an ideal method to treat cancer because it can break the immunotolerance of tumor and induce robust immunoresponse. However, constructing a wide antigen-adaptive, easy-handling, and biodegradable system that can recruit and activate antigen-presenting cells (APCs) much effectively is still a challenge. Herein, we show an injectable DNA supramolecular hydrogel vaccine (DSHV) system which could efficiently recruit and activate APCs in vitro and in vivo. The in vitro processes have been visualized by fluorescence microscopy. Through intraperitoneal or subcutaneous injection, the DSHV system can mimic the function of a lymph node where the APCs are recruited and activated by the high local concentration of cytosine-phosphate-guanine. Subsequently, strong immune response and obvious antitumor effects have been obtained. Our findings demonstrated that the DSHV system could serve as a general platform for tumor vaccination and benefit the personalized cancer therapy in the near future.

We propose a framework for automated detection of dry age-related macular degeneration (AMD) and diabetic macular edema (DME) from retina optical coherence tomography (OCT) images, based on sparse coding and dictionary learning. The study aims to improve the classification performance of state-of-the-art methods. First, our method presents a general approach to automatically align and crop retina regions; then it obtains global representations of images by using sparse coding and a spatial pyramid; finally, a multiclass linear support vector machine classifier is employed for classification. We apply two datasets for validating our algorithm: Duke spectral domain OCT (SD-OCT) dataset, consisting of volumetric scans acquired from 45 subjects—15 normal subjects, 15 AMD patients, and 15 DME patients; and clinical SD-OCT dataset, consisting of 678 OCT retina scans acquired from clinics in Beijing—168, 297, and 213 OCT images for AMD, DME, and normal retinas, respectively. For the former dataset, our classifier correctly identifies 100%, 100%, and 93.33% of the volumes with DME, AMD, and normal subjects, respectively, and thus performs much better than the conventional method; for the latter dataset, our classifier leads to a correct classification rate of 99.67%, 99.67%, and 100.00% for DME, AMD, and normal images, respectively.

The T-helper epitope peptide P30 (green in the scheme) from tetanus toxoid was used as the immunostimulant in MUC1 glycopeptide antitumor vaccines and apparently also acts as a built-in adjuvant. P30-conjugated glycopeptide vaccines containing three glycans in the immunodominant motifs PDTRP and GSTAP induced much stronger immune responses and complement dependent cytotoxicity mediated killing of tumor cells when applied in plain PBS solution without complete Freund's adjuvant.

Glycopeptides of tumor-associated mucin MUC1 are promising target structures for the development of antitumor vaccines. Because these endogenous structures were weakly immunogenic, they were coupled to immune-response-stimulating T-cell epitopes and the Pam(3)Cys lipopeptide to induce strong immune responses in mice. A new thioether-ligation method for the synthesis of two- and three-component vaccines that contain MUC1 glycopeptides as the B-cell epitopes, a T-cell epitope peptide, and the Pam(3)CSK(4) lipopeptide is described. The resulting fully synthetic vaccines were used for the vaccination of mice, either in a liposome with Freund's adjuvant or in aqueous PBS buffer. The three-component vaccines that contained the Tetanus Toxoid P2 T-cell epitope peptide induced strong immune responses, even when administered just in PBS. By activation of the complement-dependent cytotoxicity (CDC) complex, the antisera induced the killing of tumor cells.

A shot in the arm for anticancer vaccines: Synthetic MUC1 glycopeptides bearing the STn and 2,6‐ST antigens were conjugated covalently to BSA (see scheme). The obtained synthetic vaccines induced very strong immune responses in Balb/c mice. Predominant IgG isotype antibodies were induced. The antibodies exhibited strong binding to breast cancer cells of the MCF‐7 cell line.

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