Dendritic cell-directed lentivector vaccine induces antigen-specific immune responses against murine melanoma

Yang, Haiguang; Hu, Biliang; Liang, Xiao; Wang, P

doi:10.1038/cgt.2011.13

Cited by 22 publications

(16 citation statements)

References 59 publications

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“…As shown in Figure 1B, approximately 60% of the 293T.DC-SIGN cells displayed PSCA expression post-DCLV-PSCA transduction, whereas only 6.79% were PSCA-positive in the 293T cells. The specificity observed here is consistent with previous reports showing the ability of DCLV to preferentially transduce DC-SIGN-expressing cells [41], [44]. We further investigated whether DCLV-PSCA could target and mediate PSCA expression in bone marrow-derived DCs (BMDCs).…”

Section: Resultssupporting

confidence: 91%

“…injections resulted in a much lower response (<0.5%). This response trend is consistent with results from immunization with DCLV encoding HIV-1 Gag [45] or human gp100 [44]. Based on the i.d.…”

Section: Resultssupporting

confidence: 87%

“…They are able to transduce and activate DCs in vivo and mediate durable transgene expression, which can be subsequently processed by DCs and presented to T cells as antigens [49]. Additionally, these vectors are engineered to be non-replicable, with minimal viral proteins being expressed, and, therefore, less anti-vector immunity was found [44]. Furthermore, because of DC-specific transduction, fewer safety and off-target concerns arise when DCs are applied as vaccine vehicles in vivo [41].…”

Section: Discussionmentioning

confidence: 99%

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Dendritic Cell-Directed Vaccination with a Lentivector Encoding PSCA for Prostate Cancer in Mice

et al. 2012

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Many studies have demonstrated that prostate stem cell antigen (PSCA) is an attractive target for immunotherapy based on its overexpression in prostate tumor tissue, especially in some metastatic tissues. In this study, we evaluated dendritic cell (DC)-directed lentiviral vector (DCLV) encoding murine PSCA (DCLV-PSCA) as a novel tumor vaccine for prostate cancer in mouse models. We showed that DCLV-PSCA could preferentially deliver the PSCA antigen gene to DC-SIGN-expressing 293T cells and bone marrow-derived DCs (BMDCs). Direct immunization with the DCLV-PSCA in male C57BL/6 mice elicited robust PSCA-responsive CD8+ and CD4+ T cells in vivo. In a transgenic adenocarcinoma mouse prostate cell line (TRAMP-C1) synergetic tumor model, we further demonstrated that DCLV-PSCA-vaccinated mice could be protected from lethal tumor challenge in a prophylactic model, whereas slower tumor growth was observed in a therapeutic model. This DCLV-PSCA vaccine also showed efficacy in inhibiting tumor metastases using a PSCA-expressing B16-F10 model. Taken together, these data suggest that DCLV is a potent vaccine carrier for PSCA in delivering anti-prostate cancer immunity.

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Section: Resultssupporting

confidence: 91%

Section: Resultssupporting

confidence: 87%

Section: Discussionmentioning

confidence: 99%

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Dendritic Cell-Directed Vaccination with a Lentivector Encoding PSCA for Prostate Cancer in Mice

et al. 2012

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“…In addition, other strategies include encapsulating peptides in biodegradable polymers that are phagocytized by DCs [127], preparing DCs fused with tumor cells [128], or pulsing DCs with RNA encoding tumor antigens [129]. In recent years, the use of lentiviruses to induce stable transduction of DCs has also been successfully evaluated [130–132]. These vectors have the advantage of infecting nondividing cells, thus being excellent tools to express different molecules in DCs.…”

Section: Dendritic Cells and Antitumor Therapymentioning

confidence: 99%

Dendritic Cells The Tumor Microenvironment and the Challenges for an Effective Antitumor Vaccination

Benencia

Sprague

McGinty

et al. 2012

Journal of Biomedicine and Biotechnology

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Many clinical trials have been carried out or are in progress to assess the therapeutic potential of dendritic-cell- (DC-) based vaccines on cancer patients, and recently the first DC-based vaccine for human cancer was approved by the FDA. Herewith, we describe the general characteristics of DCs and different strategies to generate effective antitumor DC vaccines. In recent years, the relevance of the tumor microenvironment in the progression of cancer has been highlighted. It has been shown that the tumor microenvironment is capable of inactivating various components of the immune system responsible for tumor clearance. In particular, the effect of the tumor microenvironment on antigen-presenting cells, such as DCs, does not only render these immune cells unable to induce specific immune responses, but also turns them into promoters of tumor growth. We also describe strategies likely to increase the efficacy of DC vaccines by reprogramming the immunosuppressive nature of the tumor microenvironment.

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“…Previous work in our laboratory has shown that LV pseudotyped with a modified Sindbis glycoprotein can directly target DC-SIGN on the surface of DCs [10]. This targeting was able to elicit a stronger immune response than a non-targeted vector [11]. Here, we sought to utilize LV to deliver breast cancer antigens to DCs in order to stimulate the host’s immune response against a tumor.…”

Section: Introductionmentioning

confidence: 99%

Breast cancer vaccines delivered by dendritic cell-targeted lentivectors induce potent antitumor immune responses and protect mice from mammary tumor growth

Bryson

Han

Truong

et al. 2017

Vaccine

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Breast cancer immunotherapy is a potent treatment option, with antibody therapies such as trastuzumab increasing 2-year survival rates by 50%. However, active immunotherapy through vaccination has generally been clinically ineffective. One potential means of improving vaccine therapy is by delivering breast cancer antigens to dendritic cells (DCs) for enhanced antigen presentation. To accomplish this in vivo, we pseudotyped lentiviral vector (LV) vaccines with a modified Sindbis Virus glycoprotein so that they could deliver genes encoding the breast cancer antigen alpha-lactalbumin (Lalba) or erb-b2 receptor tyrosine kinase 2 (ERBB2 or HER2) directly to resident DCs. We hypothesized that utilizing these DC-targeting lentiviral vectors as a breast cancer vaccine could lead to an improved immune response against self-antigens found in breast cancer tumors. Indeed, single injections of the vaccine vectors were able to amplify antigen-specific CD8 T cells 4–6 fold over naïve mice, similar to the best published vaccine regimens. Immunization of these mice completely inhibited tumor growth in a foreign antigen environment (LV-ERBB2 in wildtype mice), and it reduced the rate of tumor growth in a self-antigen environment (LV-Lalba in wildtype or LV-ERBB2 in MMTV-huHER2 transgenic). These results show that a single injection with targeted lentiviral vectors can be an effective immunotherapy for breast cancer. Furthermore, they could be combined with other immunotherapeutic regimens to improve outcomes for patients with breast cancer.

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Dendritic cell-directed lentivector vaccine induces antigen-specific immune responses against murine melanoma

Cited by 22 publications

References 59 publications

Dendritic Cell-Directed Vaccination with a Lentivector Encoding PSCA for Prostate Cancer in Mice

Dendritic Cell-Directed Vaccination with a Lentivector Encoding PSCA for Prostate Cancer in Mice

Dendritic Cells The Tumor Microenvironment and the Challenges for an Effective Antitumor Vaccination

Breast cancer vaccines delivered by dendritic cell-targeted lentivectors induce potent antitumor immune responses and protect mice from mammary tumor growth

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