Recombinant lentivector as a genetic immunization vehicle for antitumor immunity

He, Yukai; Munn, David H.; Falo, Louis D.

doi:10.1586/14760584.6.6.913

Cited by 23 publications

(22 citation statements)

References 100 publications

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“…Lentivirus-based vectors have several properties that offer distinct advantages over current vectors used in clinical trials [99,100]. Lentivirus-based vectors are typically less immunogenic as most genes encoding viral proteins have been removed, thereby allowing for the repeated use of these vectors for immunization without inducing pre-existing immune responses against the vector.…”

Section: Bacterial and Viral Vectorsmentioning

confidence: 99%

Directing Dendritic Cell Immunotherapy Towards Successful Cancer Treatment

2009

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The use of dendritic cells (DCs) for tumor immunotherapy represents a powerful approach for harnessing the patient's own immune system to eliminate tumor cells. However, suboptimal conditions for generating potent immunostimulatory DCs, as well as the induction of tolerance and suppression mediated by the tumors and its microenvironment have contributed to limited success. Combining DC vaccines with new approaches that enhance immunogenicity and overcome the regulatory mechanisms underlying peripheral tolerance may be the key to achieving effective and durable anti-tumor immune responses that translate to better clinical outcomes. Keywords dendritic cell; tumor immunotherapy; vaccinationDendritic cells (DCs) are the most potent antigen-presenting cells (APCs), capable of activating both naive and memory immune responses, and maintaining the delicate balance between immunity and tolerance. Several studies have demonstrated that antigens expressed by tumors, including tumor-specific antigens, can be loaded on DCs to trigger an immune response in vitro. Clinical trials of antigen-pulsed DCs have been conducted in patients with various types of tumors, including breast cancer, multiple myeloma, prostate cancer, renal cell carcinoma, malignant melanoma, colorectal cancer and non-small-cell lung cancer [201]. While these studies have demonstrated that antigen-loaded DC vaccines are a safe and promising therapy for tumors, their clinical efficacy remains to be established. The first part of this review discusses human DC biology and the second part focuses on the application of DCs for harnessing for anti-tumor immunity. DC biologyThe combined action of both the innate and adaptive immune system is required for the development of protective immune responses. The innate immune response serves as the initial defense against pathogenic organisms or neoplastic cell growth by providing a local and

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Section: Bacterial and Viral Vectorsmentioning

confidence: 99%

Directing Dendritic Cell Immunotherapy Towards Successful Cancer Treatment

2009

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“…Therefore, lentivectors have thus been proposed to be an ideal vector tool for vaccine delivery. 20,[24][25][26][27][28][29][30][31][32][33] Based on the study of Sindbis virus, a member of the Alphavirus genus and the Togaviride family, we have reported a mutant Sindbis virus glycoprotein, (SVGmu) which can specifically bind to DC-specific intracellular adhesion molecule (ICAM) 3 grabbing non-integrin (DC-SIGN, CD209). 34 DC-SIGN is a C-type lectin-like receptor and is expressed on DCs and macrophages.…”

Section: Introductionmentioning

confidence: 99%

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

Yang

Liang

et al. 2011

Cancer Gene Ther

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Lentivectors are potential vaccine delivery vehicles because they can efficiently transduce a variety of non-dividing cells, including antigen-presenting cells, and do not cause expression of extra viral proteins. To improve safety while retaining efficiency, a dendritic cell (DC)-specific lentivector was constructed by pseudotyping the vector with an engineered viral glycoprotein derived from Sindbis virus. We assessed the level of anti-tumor immunity conferred by this engineered lentivector encoding the melanoma antigen gp100 in a mouse model. Footpad injection of the engineered lentivectors results in the best antigen-specific immune response as compared with subcutaneous and intraperitoneal injections. A single prime vaccination of the engineered lentivectors can elicit a high frequency (up to 10%) of gp100-specific CD8 þ T cells in peripheral blood 3 weeks after the vaccination and this response will be maintained at around 5% for up to 8 weeks. We found that these engineered lentivectors elicited relatively low levels of anti-vector neutralizing antibody responses. Importantly, direct injection of this engineered lentivector inhibited the growth of aggressive B16 murine melanoma. These data suggest that DC-specific lentivectors can be a novel and alternative vaccine carrier with the potential to deliver effective anti-tumor immunity for cancer immunotherapy.

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“…Recently, we and others have shown that recombinant lentivector effectively transduced dendritic cells (DCs) in vitro and in vivo and stimulated more potent and longer lasting Ag-specific CD8 T cell immune responses than other viral vectors, as well as other genetic immunization approaches such as naked plasmid DNA (12–17). The potency and durability of lentivector-induced immune responses may be related to the vector’s capacity to efficiently transduce nondividing skin DC subsets without compromising their Ag processing and presenting function in vivo (12, 18, 19).…”

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confidence: 99%

Lentivector Immunization Stimulates Potent CD8 T Cell Responses against Melanoma Self-Antigen Tyrosinase-Related Protein 1 and Generates Antitumor Immunity in Mice

Liu

Peng²,

et al. 2009

The Journal of Immunology

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Recombinant lentivector immunization has been demonstrated to induce potent CD8 T cell responses in vivo. In this study, we investigated whether lentivector delivering a self/tumor Ag, tyrosinase related protein 1 (TRP1), could stimulate effective antitumor T cell responses. We found that immunization with lentivector expressing mutated TRP1 Ag elicited potent CD8 T cell responses against multiple TRP1 epitopes. Importantly, the activated CD8 T cells effectively recognize wild-type TRP1 epitopes. At peak times, as many as 10% of CD8 T cells were effector cells against TRP1 Ag. These cells killed wild-type TRP1 peptide-pulsed target cells in vivo and produced IFN-γ after ex vivo stimulation. The CD8 T cell responses were long-lasting (3–4 wk). Immunized mice were protected from B16 tumor cell challenge. In a therapeutic setting, lentivector immunization induced potent CD8 T cell responses in tumor bearing mice. The number of infiltrating T cells and the ratio of CD8/CD4 were dramatically increased in the tumors of immunized mice. The tumor-infiltrating CD8 T cells were functional and produced IFN-γ. The potent CD8 T cell responses stimulated by lentivector immunization eliminated small 3-day s.c. B16 tumors and strongly inhibited the growth of more established 5-day tumors. These studies demonstrate that genetic immunization with lentivector expressing mutated self/tumor Ag can generate potent CD8 T cell immune responses and antitumor immunity that prevent and inhibit B16 tumor growth, suggesting that lentivector immunization has the potential for tumor immunotherapy and immune prevention.

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Recombinant lentivector as a genetic immunization vehicle for antitumor immunity

Cited by 23 publications

References 100 publications

Directing Dendritic Cell Immunotherapy Towards Successful Cancer Treatment

Directing Dendritic Cell Immunotherapy Towards Successful Cancer Treatment

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

Lentivector Immunization Stimulates Potent CD8 T Cell Responses against Melanoma Self-Antigen Tyrosinase-Related Protein 1 and Generates Antitumor Immunity in Mice

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