Tumor suppressive efficacy through augmentation of tumor-infiltrating immune cells by intratumoral injection of chemokine-expressing adenoviral vector

Okada, Naoki; Sasaki, Akinori; Niwa, Masakazu; Okada, Yoshiaki; Hatanaka, Yutaka; Tani, Yoichi; Mizuguchi, Hiroyuki; Nakagawa, Shinsaku; Fujita, Takuya; Yamamoto, Akira

doi:10.1038/sj.cgt.7700903

Cited by 42 publications

(43 citation statements)

References 46 publications

(44 reference statements)

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“…[22][23][24][25] in cancer mouse models. The ambivalent role of these chemokines is confirmed by the fact that CCL22 has been associated with tumor regression in mouse models (20,21,26) and good prognosis in human lung cancer (27), whereas its expression correlates with Treg infiltration and poor prognosis in breast cancer (23). Because many Ti-BALT T cells express CCR4 and Ti-BALT contains very few Treg (data not shown), we hypothesize that this receptor would recruit mostly other T-cell subtypes in these structures.…”

Section: Discussionmentioning

confidence: 78%

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Characterization of Chemokines and Adhesion Molecules Associated with T cell Presence in Tertiary Lymphoid Structures in Human Lung Cancer

et al. 2011

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De novo formation of tertiary lymphoid structures (TLS) has been described in lung cancers. Intratumoral TLS seem to be functional and are associated with a long-term survival for lung cancer patients, suggesting that they represent an activation site for tumor-specific T cells. Here, we characterized T-cell recruitment to TLS in human lung cancer to identify the adhesion molecules and chemoattractants orchestrating this migration. We found that most TLS T cells were CD62Lþ and mainly of CD4þ memory phenotype, but naive T cells were highly enriched in these structures as compared with the rest of the tumor. A specific gene expression signature associated with T cell presence was identified in TLS, which included chemokines (CCL19, CCL21, CXCL13, CCL17, CCL22, and IL16), adhesion molecules (ICAM-2, ICAM-3, VCAM-1, and MAdCAM-1) and integrins (alphaL, alpha4, and alphaD). The presence of the corresponding receptors on TLS T cells was confirmed. Intratumoral PNAdþ high endothelial venules also were exclusively associated with TLS and colocalized with CD62Lþ lymphocytes. Together, these data bring new insights into the T-cell recruitment to intratumoral TLS and suggest that blood T cell enter into TLS via high endothelial venules, which represent a new gateway for T cells to the tumor. Findings identify the molecules that mediate migration of tumor-specific T cells into TLS where T cell priming occurs, suggesting new strategies to enhance the efficacy of cancer immunotherapies.

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Section: Discussionmentioning

confidence: 78%

“…Expression of CCR4 and its ligands, CCL17 and CCL22, was found in Ti-BALT at the mRNA and protein levels. The CCL17 and CCL22 chemokines have been shown to recruit effector T cells (19)(20)(21)(22), as well as regulatory T cells (Treg; refs. [22][23][24][25] in cancer mouse models.…”

Section: Discussionmentioning

confidence: 99%

Characterization of Chemokines and Adhesion Molecules Associated with T cell Presence in Tertiary Lymphoid Structures in Human Lung Cancer

et al. 2011

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“…A different approach is the coexpression of chemoattractant molecules by a genetic vaccine to recruit APCs to the site of vaccine delivery. This approach has been studied in immunotherapy of tumors (16,19,34,46) and also for vaccination against virus infections (5, 13, 26, 47), but it has not yet been tested in a retrovirus challenge model.In this vaccination study we sought to increase the presence of DCs at the site of vaccine delivery. For this, we coadministered adenovirus vectors encoding different chemokines along with viral antigens.…”

mentioning

confidence: 99%

Codelivery of the Chemokine CCL3 by an Adenovirus-Based Vaccine Improves Protection from Retrovirus Infection

Lietz

Bayer

Ontikatze

et al. 2012

J Virol

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. After antigen uptake and activation, DCs mature and migrate to lymphoid tissues, where they present antigen-derived peptides on major histocompatibility complex type II (MHC-II) molecules and provide stimulatory signals for antigen-specific T cells. Because of the important role of DCs in the induction of protective immunity, DC targeting of antigens has been a much-pursued strategy in the development of genetic and protein-based vaccines. For this, vaccine antigens were fused to antibodies or ligands of DC surface molecules and delivered directly as a protein vaccine or through encoding DNA in a genetic plasmid-or viral vectorbased vaccine regimen (4,33,37,43,44). A different approach is the coexpression of chemoattractant molecules by a genetic vaccine to recruit APCs to the site of vaccine delivery. This approach has been studied in immunotherapy of tumors (16,19,34,46) and also for vaccination against virus infections (5, 13, 26, 47), but it has not yet been tested in a retrovirus challenge model.In this vaccination study we sought to increase the presence of DCs at the site of vaccine delivery. For this, we coadministered adenovirus vectors encoding different chemokines along with viral antigens. Chemokines are a group of proinflammatory proteins of 6 to 14 kDa that act as ligands of G-protein-coupled receptors (reviewed in reference 31) expressed on leukocytes. Chemokines induce the migration of these cells and play an important role in both homeostasis and inflammation. For these different processes, some chemokines are expressed continuously in certain tissues, while others are only expressed in response to inflammatory stimuli. Depending on the expression of their respective receptors, chemokines can stimulate multiple cell types. In the present study we studied the effects of the chemokines CCL3, CCL20, CCL21, and CXCL14 on immune responses induced by an adenovirus-based vaccine. All four tested chemokines, while acting on differing ranges of target cells, are known to be chemoattractants for DCs (reviewed in reference 48).We analyzed the adjuvant effect of chemokines for retroviral immunity using an HIV vaccination mouse model and the Friend retrovirus (FV) model. FV is an immunosuppressive retroviral complex, consisting of the apathogenic Friend murine leukemia virus (F-MuLV) and the replication-defective but pathogenic spleen focus-forming virus, that causes splenomegaly and lethal erythroleukemia in susceptible mice (15). In contrast to the vaccination against HIV proteins, the FV model allows for challenging immunized mice with a pathogenic retrovirus. The FV infection model has offered valuable insights into the role of particular cell types in the immune response to a retroviral infection and into the basic requirements for immune protection. Using attenuated F-MuLV helper virus, it was demonstrated that complete protection from lethal FV challenge requires both humoral and cellular responses, comprising antibodies and CD4 ϩ and CD8 ϩ T cells (10). Although the correlates of immune protection ...

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“…Thus, to evaluate the potential of in vivo chemokine gene therapy for cancer using the AdRGD vector system, we investigated the tumor-suppressive effects and accumulation of tumor-associated immune cells in mice directly injected with chemokine-expressing AdRGD vector in established B16BL6 melanoma tissue. 68) This review focuses on the results of intratumoral injection of the AdRGD vector encoding the chemokine CC chemokine ligand-17 (CCL17) and CCL19.…”

Section: Chemokine Gene Therapy For Enhancing Accumulation Of Immune mentioning

confidence: 99%

“…Thus we examined the antitumor effect in B16BL6-bearing mice treated with intradermal immunization of DCs transduced with gp100 by the AdRGD vector, followed by intratumoral injection of AdRGD-CCL17 or AdRGD-CCL19. 68) To confirm the activation of systemic immunity in tumor-bearing mice immunized with gp100/DCs, we evaluated CTL activity in splenocytes from these mice. Single immunization with gp100/DCs at a site distant from the tumor inoculation site could promote killing activity of effector cells targeting B16BL6 cells.…”

Section: Chemokine Gene Therapy For Enhancing Accumulation Of Immune mentioning

confidence: 99%

Cell Delivery System: A Novel Strategy to Improve the Efficacy of Cancer Immunotherapy by Manipulation of Immune Cell Trafficking and Biodistribution

Okada

2005

Biological & Pharmaceutical Bulletin

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Tumor cells that generally accumulate mutations in the genome express molecules different both qualitatively and quantitatively from normal cells. An immunosurveillance system for these molecules, known as the tumor-associated antigens (TAAs), plays an important role in the elimination of cancer cells during the initial stage. Although cancer immunotherapy targeting TAAs has progressed steadily with the development of various vaccine strategies, satisfactory efficacy, such as marked tumor regression and complete response, has not been previously reported in a clinical setting. To improve the therapeutic effects of cancer immunotherapy, the application of chemokine-chemokine receptor coupling, which controls the trafficking and biodistribution of immune cells in the living body, is an attractive potential approach. This review introduces our novel "cell delivery system," which employs an Arg-Gly-Asp (RGD) fiber-mutant adenovirus vector encoding the chemokine or chemokine receptor gene in cancer immunotherapy.

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Tumor suppressive efficacy through augmentation of tumor-infiltrating immune cells by intratumoral injection of chemokine-expressing adenoviral vector

Cited by 42 publications

References 46 publications

Characterization of Chemokines and Adhesion Molecules Associated with T cell Presence in Tertiary Lymphoid Structures in Human Lung Cancer

Characterization of Chemokines and Adhesion Molecules Associated with T cell Presence in Tertiary Lymphoid Structures in Human Lung Cancer

Codelivery of the Chemokine CCL3 by an Adenovirus-Based Vaccine Improves Protection from Retrovirus Infection

Cell Delivery System: A Novel Strategy to Improve the Efficacy of Cancer Immunotherapy by Manipulation of Immune Cell Trafficking and Biodistribution

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