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Chemical-free inactivated whole influenza virus vaccine prepared by ultrashort pulsed laser treatment

Tsen, Shaw-Wei David; Donthi, Nisha; La, Victor; Hsieh, Wen-Han; Li, Yen-Der; Knoff, Jayne; Chen, Alexander; Wu, Tzyy-Choou; Hung, Chien-Fu; Achilefu, Samuel; Tsen, Kong-Thon
There is an urgent need for rapid methods to develop vaccines in response to emerging viral pathogens. Whole inactivated virus (WIV) vaccines represent an ideal strategy for this purpose; however, a universal method for producing safe and immunogenic inactivated vaccines is lacking. Conventional pathogen inactivation methods such as formalin, heat, ultraviolet light, and gamma rays cause structural alterations in vaccines that lead to reduced neutralizing antibody specificity, and in some cases, disastrous T helper type 2-mediated immune pathology. We have evaluated the potential of a visible ultrashort pulsed (USP) laser method to generate safe and immunogenic WIV vaccines without adjuvants. Specifically, we demonstrate that vaccination of mice with laser-inactivated H1N1 influenza virus at about a 10-fold lower dose than that required using conventional formalin-inactivated influenza vaccines results in protection against lethal H1N1 challenge in mice. The virus, inactivated by the USP laser irradiation, has been shown to retain its surface protein structure through hemagglutination assay. Unlike conventional inactivation methods, laser treatment did not generate carbonyl groups in protein, thereby reducing the risk of adverse vaccine-elicited T helper type 2 responses. Therefore, USP laser treatment is an attractive potential strategy to generate WIV vaccines with greater potency and safety than vaccines produced by current inactivation techniques.
PMID: 25423046
ISSN: 1560-2281
CID: 3156892

Innovative DNA vaccine to break immune tolerance against tumor self-antigen

Kang, Tae Heung; Mao, Chih-Ping; La, Victor; Chen, Alexander; Hung, Chien-Fu; Wu, T-C
Vaccination is, in theory, a safe and effective approach for controlling disseminated or metastatic cancer due to the specificity of the mammalian immune system, yet its success in the clinic has been hampered thus far by the problem of immune tolerance to tumor self-antigen. Here we describe a DNA vaccination strategy that is able to control cancer by overcoming immune tolerance to tumor self-antigen. We engineered a DNA construct encoding a dimeric form of a secreted single-chain trimer of major histocompatibility complex class I heavy chain, β2-microglobulin, and peptide antigen linked to immunoglobulin G (SCT-Ag/IgG). The chimeric protein was able to bind to antigen-specific CD8(+) T cells with nearly 100% efficiency and strongly induce their activation and proliferation. In addition, the chimeric protein was able to coat professional antigen-presenting cells through the F(c) receptor to activate antigen-specific CD8(+) T cells. Furthermore, intradermal vaccination with DNA-encoding SCT-Ag/IgG could generate significant numbers of cytotoxic effector T cells against tumor self-antigen and leads to successful therapeutic outcomes in a preclinical model of metastatic melanoma. Our data suggest that the DNA vaccine strategy described in the current study is able to break immune tolerance against endogenous antigen from melanoma and result in potent therapeutic antitumor effects. Such strategy may be used in other antigenic systems for the control of infections and/or cancers.
PMID: 23268564
ISSN: 1557-7422
CID: 3156882

Tumor-targeted delivery of IL-2 by NKG2D leads to accumulation of antigen-specific CD8+ T cells in the tumor loci and enhanced anti-tumor effects

Kang, Tae Heung; Mao, Chih-Ping; He, Liangmei; Tsai, Ya-Chea; Liu, Katherine; La, Victor; Wu, T-C; Hung, Chien-Fu
Interleukin-2 (IL-2) has been shown to promote tumor-specific T-cell proliferation and differentiation but systemic administration of IL-2 results in significant toxicity. Therefore, a strategy that can specifically deliver IL-2 to the tumor location may alleviate concerns of toxicity. Because NKG2D ligands have been shown to be highly expressed in many cancer cells but not in healthy cells, we reason that a chimeric protein consisting of NKG2D linked to IL-2 will lead to the specific targeting of IL-2 to the tumor location. Therefore, we created chimeric proteins consisting of NKG2D linked to Gaussia luciferase (GLuc; a marker protein) or IL-2 to form NKG2D-Fc-GLuc and NKG2D-Fc-IL2, respectively. We demonstrated that NKG2D linked to GLuc was able to deliver GLuc to the tumor location in vivo. Furthermore, we showed that TC-1 tumor-bearing mice intramuscularly injected with DNA encoding NKG2D-Fc-IL2, followed by electroporation, exhibited an increased number of luciferase-expressing E7-specific CD8+ T cells at the tumor location. More importantly, treatment with the DNA construct encoding NKG2D-Fc-IL2 significantly enhanced the therapeutic anti-tumor effects generated by intradermal vaccination with therapeutic HPV DNA in tumor-bearing mice. Therefore, by linking NKG2D to IL2, we are able to specifically deliver IL-2 to the tumor location, enhancing antigen-specific T-cell immune response and controlling tumor growth. Our approach represents a platform technology to specifically deliver proteins of interest to tumor loci.
PMID: 22509395
ISSN: 1932-6203
CID: 3156872

Ectopic pregnancy in a cesarean section scar [Case Report]

Chiang, An-Jen; La, Victor; Chou, Chen-Pin; Wang, Peng-Hui; Yu, Ken-Jen
A combination of systemic chemotherapy, feticide with intrachest and intra-abdominal injection with methotrexate, and hysteroscopy with dilation and curettage to remove the gestational tissue was successful in the treatment of a cesarean scar ectopic pregnancy. This case presents images of the ultrasound, magnetic resonance imaging, and pathologic features unique to a cesarean scar pregnancy.
PMID: 21497339
ISSN: 1556-5653
CID: 3156862

Squamous cell carcinoma arising from mature cystic teratoma of the ovary [Case Report]

Chiang, An-Jen; La, Victor; Peng, Jiaqi; Yu, Ken-Jen; Teng, Nelson N H
OBJECTIVE:Squamous cell carcinoma (SCC) is the most common type of malignant transformation in mature cystic teratoma (MCT) of the ovary. The SCC is difficult to preoperatively diagnose. We conducted a retrospective study to seek the possible risk/prognostic factors and treatments for SCC arising from MCT of the ovary. METHODS:Using an institutional database, we identified 3 women treated for SCC arising from an MCT of the ovary at the Kaohsiung Veteran General Hospital. A retrospective chart review was conducted, with information obtained from radiographs, operative reports, pathology reports, and radiation oncology records. RESULTS:A total of 1551 cases of MCT were diagnosed at Kaohsiung Veteran General Hospital from 1990 to 2009, of which, malignant teratoma SCC type was noted in 3 cases (0.19%). The median age of the subjects was 39 years. Abdominal fullness was the most common symptom (3/3 cases). The mean diameter of the ovarian tumor was 17.3 cm, ranging from 16 to 18 cm. All 3 patients received simple right salpingo-oophorectomy or debulking surgery. Two of the patients reached stage IIIC and died. CONCLUSIONS:: With our review as basis, we recommend being cautious of the following risk factors: patient age, tumor size, ultrasound characteristics, sonar tumor vessel wave form, computed tomography, and levels of SCC and CA125 tumor markers. We suggest that patients have regular ovarian ultrasound examination. Based on our literature review, stage IA patients who undergo standardized operational procedures do well without adjuvant treatment, but such patients must be confirmed accurately with complete surgical staging to be in stage IA before undergoing conservative management. The optimal approach to the management of patients with advanced stage and recurrent disease is unclear. Surgical cytoreduction with proper staging, adjuvant therapy with platinum-based or paclitaxel-based chemotherapy, and concurrent whole pelvic radiation have been recommended as possible methods of treatment.
PMID: 21430455
ISSN: 1525-1438
CID: 3156852