Sindbis Viral Vectors Transiently Deliver Tumor-associated Antigens to Lymph Nodes and Elicit Diversified Antitumor CD8+ T-cell Immunity

Granot, Tomer; Yamanashi, Yoshihide; Meruelo, Daniel

doi:10.1038/mt.2013.215

Cited by 42 publications

(51 citation statements)

References 42 publications

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“…9 ). To assess whether Y27632 promotes an immune response against tumour-associated antigens, we isolated tumour-draining lymph node (LN) cells from CT26.CL25-mCherry tumour-bearing mice, and analysed their immune response against β-galactosidase (β-gal), a model tumour-associated antigen in CT26.CL25 cells 28 . Tumour-draining LN cells from Y27632-treated mice produced more interferon-γ (IFN-γ) in response to a β-gal peptide than those from vehicle-treated mice, an effect that was abrogated by phagocyte depletion (Fig.…”

Section: Resultsmentioning

confidence: 99%

Combined Rho-kinase inhibition and immunogenic cell death triggers and propagates immunity against cancer

et al. 2018

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Activation of T cell immune response is critical for the therapeutic efficacy of cancer immunotherapy. Current immunotherapies have shown remarkable clinical success against several cancers; however, significant responses remain restricted to a minority of patients. Here, we show a therapeutic strategy that combines enhancing the phagocytic activity of antigen-presenting cells with immunogenic cell death to trigger efficient antitumour immunity. Rho-kinase (ROCK) blockade increases cancer cell phagocytosis and induces antitumour immunity through enhancement of T cell priming by dendritic cells (DCs), leading to suppression of tumour growth in syngeneic tumour models. Combining ROCK blockade with immunogenic chemotherapy leads to increased DC maturation and synergistic CD8+ cytotoxic T cell priming and infiltration into tumours. This therapeutic strategy effectively suppresses tumour growth and improves overall survival in a genetic mouse mammary tumour virus/Neu tumour model. Collectively, these results suggest that boosting intrinsic cancer immunity using immunogenic killing and enhanced phagocytosis is a promising therapeutic strategy for cancer immunotherapy.

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Section: Resultsmentioning

confidence: 99%

Combined Rho-kinase inhibition and immunogenic cell death triggers and propagates immunity against cancer

et al. 2018

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“…To explore the in vivo therapeutic potential of FHSirpα alone, we evaluated the immunotherapeutic antitumor activity of FHSirpα using the CT26.CL25 colon carcinoma cell line, a tumor antigen β‐galactosidase (β‐gal)‐expressing cell model, in syngeneic BALB/c immunocompetent mice (Figure S13, Supporting Information). Treatment with FHSirpα slowed tumor growth rates, whereas no substantial inhibition was observed upon treatment with mSirpα (Figure e; Figure S14, Supporting Information).…”

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confidence: 99%

Nanocage‐Therapeutics Prevailing Phagocytosis and Immunogenic Cell Death Awakens Immunity against Cancer

et al. 2018

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A growing appreciation of the relationship between the immune system and the tumorigenesis has led to the development of strategies aimed at "re-editing" the immune system to kill tumors. Here, a novel tactic is reported for overcoming the activation-energy threshold of the immunosuppressive tumor microenvironment and mediating the delivery and presentation of tumor neoantigens to the host's immune system. This nature-derived nanocage not only efficiently presents ligands that enhance cancer cell phagocytosis, but also delivers drugs that induce immunogenic cancer cell death. The designed nanocage-therapeutics induce the release of neoantigens and danger signals in dying tumor cells, and leads to enhancement of tumor cell phagocytosis and cross-priming of tumor specific T cells by neoantigen peptide-loaded antigen-presenting cells. Potent inhibition of tumor growth and complete eradication of tumors is observed through systemic tumor-specific T cell responses in tumor draining lymph nodes and the spleen and further, infiltration of CD8+ T cells into the tumor site. Remarkably, after removal of the primary tumor, all mice treated with this nanocage-therapeutics are protected against subsequent challenge with the same tumor cells, suggesting development of lasting, tumor-specific responses. This designed nanocage-therapeutics "awakens" the host's immune system and provokes a durable systemic immune response against cancer.

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“…Only a single intratumoral injection of 1 μg of SFV-LacZ RNA resulted in 10–20 days of survival extension in mice with existing tumors. Similarly, SIN-LacZ vectors demonstrated therapeutic efficacy in a mouse CT26 colon carcinoma model [101]. Despite not targeting specifically CT26 cells, SIN vectors showed susceptibility to mediastinal lymph nodes (MLNs), which induced effector and memory CD8+ T-cells displaying robust cytotoxicity.…”

Section: Self-replicating Rna Virus-based Vaccinesmentioning

confidence: 99%

Replicon RNA Viral Vectors as Vaccines

Lundström¹

2016

Vaccines

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Single-stranded RNA viruses of both positive and negative polarity have been used as vectors for vaccine development. In this context, alphaviruses, flaviviruses, measles virus and rhabdoviruses have been engineered for expression of surface protein genes and antigens. Administration of replicon RNA vectors has resulted in strong immune responses and generation of neutralizing antibodies in various animal models. Immunization of mice, chicken, pigs and primates with virus-like particles, naked RNA or layered DNA/RNA plasmids has provided protection against challenges with lethal doses of infectious agents and administered tumor cells. Both prophylactic and therapeutic efficacy has been achieved in cancer immunotherapy. Moreover, recombinant particles and replicon RNAs have been encapsulated by liposomes to improve delivery and targeting. Replicon RNA vectors have also been subjected to clinical trials. Overall, immunization with self-replicating RNA viruses provides high transient expression levels of antigens resulting in generation of neutralizing antibody responses and protection against lethal challenges under safe conditions.

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Sindbis Viral Vectors Transiently Deliver Tumor-associated Antigens to Lymph Nodes and Elicit Diversified Antitumor CD8+ T-cell Immunity

Cited by 42 publications

References 42 publications

Combined Rho-kinase inhibition and immunogenic cell death triggers and propagates immunity against cancer

Combined Rho-kinase inhibition and immunogenic cell death triggers and propagates immunity against cancer

Nanocage‐Therapeutics Prevailing Phagocytosis and Immunogenic Cell Death Awakens Immunity against Cancer

Replicon RNA Viral Vectors as Vaccines

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