Improved efficacy of therapeutic vaccination with viable human umbilical vein endothelial cells against murine melanoma by introduction of OK432 as adjuvant

Xu, Maolei; Xing, Yun; Zhou, Ling; Yang, Xue; Yao, Wenjun; Xiao, Wen; Ge, Chiyu; Ma, Yanju; Yang, Jie; Wu, Jie; Cao, Ruihua; Li, Taiming; Liu, Jingjing

doi:10.1007/s13277-012-0616-8

Cited by 10 publications

(6 citation statements)

References 28 publications

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“…Therefore, inhibition of angiogenesis is currently being studied as a new anticancer therapy. Since the first vaccine targeting tumor angiogenesis was reported, proliferative HUVECs as a vaccine to induce antitumor immunity has been studied in several in vivo tumor models (5)(6)(7)(8)17,26). However, further investigation is required before the HUVEC vaccine can be used clinically, and the antitumor effect has not been studied previously in esophageal carcinoma.…”

Section: Discussionmentioning

confidence: 99%

“…It has been well established that angiogenesis forms the basis of tumor development and metastasis; thus, suppressing tumor-associated angiogenesis has become a favorable strategy for the treatment of cancer (4). Active immunization with a whole endothelial cell vaccine can control tumor size and metastasis by restraining tumor angiogenesis in mice (5). Human umbilical vein endothelial cell (HUVEC) vaccines have been effective in anti-angiogenesis immunity against melanoma, glioblastoma, colorectal cancer and hepatocellular carcinoma (5)(6)(7)(8).…”

Section: Introductionmentioning

confidence: 99%

“…Active immunization with a whole endothelial cell vaccine can control tumor size and metastasis by restraining tumor angiogenesis in mice (5). Human umbilical vein endothelial cell (HUVEC) vaccines have been effective in anti-angiogenesis immunity against melanoma, glioblastoma, colorectal cancer and hepatocellular carcinoma (5)(6)(7)(8). However, the anti-angiogenic effect of the HUVEC vaccine on ESCC is still unknown.…”

Section: Introductionmentioning

confidence: 99%

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Human umbilical vein endothelial cell vaccine suppresses the angiogenesis of esophageal squamous cell carcinoma in a humanized mouse model

et al. 2018

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The antitumor effect of the human umbilical vein endothelial cell (HUVEC) vaccine has been well documented; however, its anti‑angiogenic effects on human esophageal squamous cell carcinoma (ESCC) have yet to be studied. In the present study, a 'humanized' mouse model was established by transplanting NOD/SCID mice with human peripheral blood mononuclear cells (PBMC). After 4 weeks, the level of cluster of differentiation (CD)‑45+ human T‑lymphocytes in mouse peripheral blood was >0.1%, which indicated that mouse reconstruction and the human immune system transformation had been successful. The humanized mice were used to evaluate the anti‑angiogenic effect of the HUVEC vaccine on human ESCC. After immunization with the HUVEC vaccine for 5 consecutive weeks, the humanized mice were subcutaneously transplanted with EC9706 cells. The results indicated that the HUVEC vaccine reduced the size of human esophageal carcinoma xenografts by suppressing angiogenesis. In addition, the HUVEC‑immunized mice exhibited reduced expression of angiogenesis‑associated antigens (vascular endothelial growth factor receptor 2 and VE‑Cadherin) in the tumor specimens, and increased levels of angiogenesis‑associated antibodies in the serum. Notably, the HUVEC vaccine also increased the infiltration of human T‑lymphocytes into the spleen of humanized mice. In conclusion, the present study demonstrated the anti‑angiogenic effect of the HUVEC vaccine on ESCC in a humanized mouse model, and set an experimental foundation for the application of the HUVEC vaccine in ESCC patients.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Human umbilical vein endothelial cell vaccine suppresses the angiogenesis of esophageal squamous cell carcinoma in a humanized mouse model

et al. 2018

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“…A total of six mice of the three immunized groups in the prophylactic strategy were administered with separate vaccines every week for four consecutive weeks, and serum was collected every week following initial immunization. The anti-H22 antibodies present in the serum were evaluated using an ELISA, as described previously ( 16 ). Briefly, 96-well flat-bottomed ELISA plates were coated with 10 µg/well of whole H22 cell lysates protein.…”

Section: Methodsmentioning

confidence: 99%

Inï¿½vivo antitumor activity evaluation of cancer vaccines prepared by various antigen forms in a murine hepatocellular carcinoma model

et al. 2017

Oncol Lett

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Cancer cell vaccines with strong specificity and low tolerance have been revealed to be a promising option for oncology treatment. Various antigen forms, including tumor cell lysate and glutaraldehyde-fixed tumor cells, have been intensively used in cancer vaccine preparation. However, the most effective antigen form has not yet been identified. In the present study, the antitumor efficiency of vaccines prepared by these two antigen forms was systematically investigated. Murine H22 hepatocellular carcinoma cell lysate and glutaraldehyde-fixed H22 hepatocellular carcinoma cells were conjugated with Freund's adjuvant to prepare vaccines, H22-TCL and Fixed-H22-CELL, respectively. H22-TCL and Fixed-H22-CELL were administrated by subcutaneous immunization in prophylactic and therapeutic strategies. The results of the present study revealed that H22-TCL immunization induced more significant inhibition on tumor growth and metastasis compared with Fixed-H22-CELL injection. Furthermore, histopathological observation demonstrated that H22-TCL vaccine induced larger areas of continuous necrosis within tumors compared to the Fixed-H22-CELL vaccine, which was associated with the extent of tumor inhibition. More importantly, the H22-TCL vaccine injection elicited more evident antigen-specific antibody responses compared with the Fixed-H22-CELL injection. Splenocytes from H22-TCL vaccinated mice also exhibited a more significant T lymphocytes proliferation compared with that from Fixed-H22-CELL-treated mice. All the results indicated that whole tumor cell lysate may be a more effective antigen form in cancer vaccine preparation compared with glutaraldehyde-fixed tumor cells, which elicited more marked antigen specific humoral and cellular immune responses resulted with a superior antitumor efficiency. This would have important clinical signification for cancer vaccine preparation and serve a role in prompting this to other researchers.

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“…Our results showed that OK432 could act as an effective adjuvant to assist HUVEC to elicit a more obvious inhibition than HUVEC alone. 13 However, all the mice eventually died because of the tumor attack, suggesting that the antitumor efficiency of HUVEC-OK432 vaccine was not completely satisfactory. This indicated that the strategy of using appropriate adjuvant to enhance the antitumor efficiency of HUVEC vaccine is feasible but need further optimization.…”

mentioning

confidence: 99%

A Fixed Human Umbilical Vein Endothelial Cell Vaccine With 2 Tandem Repeats of Microbial HSP70 Peptide Epitope 407-426 As Adjuvant for Therapy of Hepatoma in Mice

Xu¹,

Zhou²,

Xie³

et al. 2015

Journal of Immunotherapy

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Various studies have indicated that vaccination with endothelial cells targeting tumor angiogenesis is an effective approach for inhibiting tumor growth and metastasis. However, our previous study about a viable human umbilical vein endothelial cell (HUVEC) vaccine demonstrated that the antitumor efficiency of the targeted therapy using HUVEC plus appropriate adjuvant is feasible but need further optimization. In this study, glutaraldehyde-fixed HUVEC, tested as another antigen form, was conjugated with 2 repeats of mycobacterial HSP70(407-426) (M2) to prepare a novel HUVEC-M2 vaccine, which was expected to have an enhanced antitumor efficacy. HUVEC-M2 was administrated in mice by subcutaneous immunization in both prophylactic and therapeutic procedures. Compared with HUVEC alone, HUVEC-M2 induced a more significant inhibition on the growth of H22 hepatocellular carcinoma in mice and prolonged the survival of H22 hepatocellular carcinoma-bearing mice in both prophylactic and therapeutic procedures. Meanwhile, specific CTLs as well as antibodies against tumor endothelium correlated well with the inhibition effect were evoked by HUVEC-M2, which indicated that antiangiogenesis was mainly responsible for the antitumor effect. Moreover, the attenuated tumor-induced angiogenesis in intradermal tumor model and reduced vessel density of the intradermal tumor in mice further confirmed the antiangiogenesis effect elicited by HUVEC-M2. All the data suggested that M2 could be used as a potent adjuvant to conjugate with glutaraldehyde-fixed HUVEC for preparing HUVEC vaccines and would have important clinical implications for adjuvant cancer therapy.

show abstract

Improved efficacy of therapeutic vaccination with viable human umbilical vein endothelial cells against murine melanoma by introduction of OK432 as adjuvant

Cited by 10 publications

References 28 publications

Human umbilical vein endothelial cell vaccine suppresses the angiogenesis of esophageal squamous cell carcinoma in a humanized mouse model

Human umbilical vein endothelial cell vaccine suppresses the angiogenesis of esophageal squamous cell carcinoma in a humanized mouse model

Inï¿½vivo antitumor activity evaluation of cancer vaccines prepared by various antigen forms in a murine hepatocellular carcinoma model

A Fixed Human Umbilical Vein Endothelial Cell Vaccine With 2 Tandem Repeats of Microbial HSP70 Peptide Epitope 407-426 As Adjuvant for Therapy of Hepatoma in Mice

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