A practical approach to pancreatic cancer immunotherapy using resected tumor lysate vaccines processed to express α-gal epitopes

Furukawa, Katsunori; Tanemura, Masahiro; Miyoshi, Eiji; Eguchi, Hidetoshi; Nagano, Hiroaki; Matsunami, Katsuyoshi; Nagaoka, Satoshi; Yamada, Daisaku; Asaoka, Tadafumi; Noda, Takehiro; Wada, Hiroshi; Kikuchi, Kôichi; Goto, Keisuke; Taniyama, Kiyomi; Mori, Masaki; Doki, Yuichiro

doi:10.1371/journal.pone.0184901

Cited by 10 publications

(6 citation statements)

References 48 publications

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“…Although in early stages of development, our vaccine combines the advantages of a tumor cell-based vaccine, i.e., targeting of multiple TAA [3][4][5][6][7][8][9][10][11][12][13][14][49][50][51][52][53], with a potentially inexpensive and time-saving vaccine preparation. By using GET to transfect the IL-12 plasmid, or any other adjuvant encoding plasmid, we bypass the ex vivo viral gene transfer used by whole cell and tumor lysate vaccines in development [3][4][5][6][7]49,54]. Namely, GET enables a highly effective gene transfer directly in vivo, which significantly shortens the time needed for the preparation of the autologous vaccine [3][4][5].…”

Section: Discussionmentioning

confidence: 99%

Development of Tumor Cell-Based Vaccine with IL-12 Gene Electrotransfer as Adjuvant

et al. 2020

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Tumor cell-based vaccines use tumor cells as a source of tumor-associated antigens. In our study, we aimed to develop and test a tumor vaccine composed of tumor cells killed by irradiation combined with in vivo interleukin-12 gene electrotransfer as an adjuvant. Vaccination was performed in the skin of B16-F10 malignant melanoma or CT26 colorectal carcinoma tumor-bearing mice, distant from the tumor site and combined with concurrent tumor irradiation. Vaccination was also performed before tumor inoculation in both tumor models and tumor outgrowth was followed. The antitumor efficacy of vaccination in combination with tumor irradiation or preventative vaccination varied between the tumor models. A synergistic effect between vaccination and irradiation was observed in the B16-F10, but not in the CT26 tumor model. In contrast, up to 56% of mice were protected from tumor outgrowth in the CT26 tumor model and none were protected in the B16-F10 tumor model. The results suggest a greater contribution of the therapeutic vaccination to tumor irradiation in a less immunogenic B16-F10 tumor model, in contrast to preventative vaccination, which has shown greater efficacy in a more immunogenic CT26 tumor model. Upon further optimization of the vaccination and irradiation regimen, our vaccine could present an alternative tumor cell-based vaccine.

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Section: Discussionmentioning

confidence: 99%

Development of Tumor Cell-Based Vaccine with IL-12 Gene Electrotransfer as Adjuvant

et al. 2020

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“…Although recent studies have reported that α-gal epitopes can improve immunogenicity in several types of cancer, the efficacy of α-gal epitopes remains controversial (40,41). The application of α-gal epitopes to induce a stronger immune response in CRC required further investigation.…”

Section: Discussionmentioning

confidence: 99%

Enhanced antitumor effect of cytotoxic T lymphocytes induced by dendritic cells pulsed with colorectal cancer cell lysate expressing α‑Gal epitopes

Xing

Zou

et al. 2019

Oncol Lett

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Colorectal cancer (CRC) is one of the most common types of gastrointestinal malignancy. Traditional therapeutic options for CRC exhibit a limited effect. Adoptive cellular therapy has emerged as a new treatment strategy for CRC. Dendritic cells (DCs) are potent antigen-presenting cells. Specific cytotoxic T lymphocytes (CTLs) activated by DCs pulsed with tumor lysate have been reported to be a safe and promising treatment approach for CRC. However, the antitumor effect of specific CTLs remains limited. The low immunogenicity of tumor-associated antigens (TAAs) is the main reason for this limited therapeutic effect. In the present study, α-gal epitopes were synthesized on the CRC cell line SW620 to increase the immunogenicity of TAAs. DCs were pulsed with α-gal-expressing tumor lysate and CTLs were activated by these DCs. The cytotoxicity of CTLs was measured in vitro. The results demonstrated that DCs pulsed with α-gal-expressing tumor lysate can increase the frequency of CD3 + CD8 + CTLs and natural killer T cells, increase the level of tumor necrosis factor-α produced by CTLs and enhance the cytotoxicity of CTLs against tumor cells. Therefore, this novel approach may be an effective treatment strategy for patients with CRC.

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“…1 ). The formation of multiple α-gal epitopes by rα1,3GT was observed on human tumor cells [89] , [90] , [91] , on influenza virus [28] , [65] , and on gp120 of HIV [27] , [29] . Synthesis of α-gal epitopes on human tumor cell membranes by the enzymatic reactions in Fig.…”

Section: Glycoengineering Of α-Gal Epitopes On Sars-cov-2 Vaccinesmentioning

confidence: 98%

Amplifying immunogenicity of prospective Covid-19 vaccines by glycoengineering the coronavirus glycan-shield to present α-gal epitopes

Galili¹

2020

Vaccine

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The many carbohydrate chains on Covid-19 coronavirus SARS-CoV-2 and its S-protein form a glycan-shield that masks antigenic peptides and decreases uptake of inactivated virus or S-protein vaccines by APC. Studies on inactivated influenza virus and recombinant gp120 of HIV vaccines indicate that glycoengineering of glycan-shields to present α-gal epitopes (Galα1-3Galβ1-4GlcNAc-R) enables harnessing of the natural anti-Gal antibody for amplifying vaccine efficacy, as evaluated in mice producing anti-Gal. The α-gal epitope is the ligand for the natural anti-Gal antibody which constitutes ~1% of immunoglobulins in humans. Upon administration of vaccines presenting α-gal epitopes, anti-Gal binds to these epitopes at the vaccination site and forms immune complexes with the vaccines. These immune complexes are targeted for extensive uptake by APC as a result of binding of the Fc portion of immunocomplexed anti-Gal to Fc receptors on APC. This anti-Gal mediated effective uptake of vaccines by APC results in 10–200-fold higher anti-viral immune response and in 8-fold higher survival rate following challenge with a lethal dose of live influenza virus, than same vaccines lacking α-gal epitopes. It is suggested that glycoengineering of carbohydrate chains on the glycan-shield of inactivated SARS-CoV-2 or on S-protein vaccines, for presenting α-gal epitopes, will have similar amplifying effects on vaccine efficacy. α-Gal epitope synthesis on coronavirus vaccines can be achieved with recombinant α1,3galactosyltransferase, replication of the virus in cells with high α1,3galactosyltransferase activity as a result of stable transfection of cells with several copies of the α1,3galactosyltransferase gene ( GGTA1 ), or by transduction of host cells with replication defective adenovirus containing this gene. In addition, recombinant S-protein presenting multiple α-gal epitopes on the glycan-shield may be produced in glycoengineered yeast or bacteria expression systems containing the corresponding glycosyltransferases. Prospective Covid-19 vaccines presenting α-gal epitopes may provide better protection than vaccines lacking this epitope because of increased uptake by APC.

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A practical approach to pancreatic cancer immunotherapy using resected tumor lysate vaccines processed to express α-gal epitopes

Cited by 10 publications

References 48 publications

Development of Tumor Cell-Based Vaccine with IL-12 Gene Electrotransfer as Adjuvant

Development of Tumor Cell-Based Vaccine with IL-12 Gene Electrotransfer as Adjuvant

Enhanced antitumor effect of cytotoxic T lymphocytes induced by dendritic cells pulsed with colorectal cancer cell lysate expressing α‑Gal epitopes

Amplifying immunogenicity of prospective Covid-19 vaccines by glycoengineering the coronavirus glycan-shield to present α-gal epitopes

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