Limits...
Immune cell recruitment and cell-based system for cancer therapy.

Gao JQ, Okada N, Mayumi T, Nakagawa S - Pharm. Res. (2007)

Bottom Line: Immune cells, such as cytotoxic T lymphocytes, natural killer cells, B cells, and dendritic cells, have a central role in cancer immunotherapy.It is well established that the basis and premise of immunotherapy is the accumulation of effective immune cells in tumor tissues.Recent characterization of various chemokines and chemokine receptors in the immune system has increased our knowledge of the regulatory mechanisms of the immune response and tolerance based on immune cell localization.

View Article: PubMed Central - PubMed

Affiliation: College of Pharmaceutical Sciences, Zhejiang University, 388 Yuhangtang Road, Hangzhou 310058, People's Republic of China. gaojianqing1029@yahoo.com.cn

ABSTRACT
Immune cells, such as cytotoxic T lymphocytes, natural killer cells, B cells, and dendritic cells, have a central role in cancer immunotherapy. Conventional studies of cancer immunotherapy have focused mainly on the search for an efficient means to prime/activate tumor-associated antigen-specific immunity. A systematic understanding of the molecular basis of the trafficking and biodistribution of immune cells, however, is important for the development of more efficacious cancer immunotherapies. It is well established that the basis and premise of immunotherapy is the accumulation of effective immune cells in tumor tissues. Therefore, it is crucial to control the distribution of immune cells to optimize cancer immunotherapy. Recent characterization of various chemokines and chemokine receptors in the immune system has increased our knowledge of the regulatory mechanisms of the immune response and tolerance based on immune cell localization. Here, we review the immune cell recruitment and cell-based systems that can potentially control the systemic pharmacokinetics of immune cells and, in particular, focus on cell migrating molecules, i.e., chemokines, and their receptors, and their use in cancer immunotherapy.

Show MeSH

Related in: MedlinePlus

Chemoattraction activity for cells expressing specific receptors in vitro induced by transfection of Ad-RGD-chemokines into A549 cells. Chemoattractant activity of culture supernatants of A549 cells transfected with each chemokine gene-carrying Ad-RGD against the stable specific chemokine receptor-expressing cells. The culture supernatants of intact A549 cells, Ad-RGD-Luc-transfected A549 (Luc/A549) cells, and chemokine gene-transduced A549 cells were prepared and diluted with the assay medium. The fractional values within the parentheses in each panel express the dilution factor. These samples and recombinant chemokines dissolved with the assay medium were added to a 24-well culture plate. Cells expressing specific receptors for CCL17 and CCL22 (L1.2/CCR4), CCL20 (L1.2/CCR6), CCL19 and CCL21 (L1.2/CCR7), CCL27 (L1.2/CCR10), XCL1 (L1.2/XCR1), or CX3CL1 (L1.2/CX3CR1) were suspended with the assay medium and placed in a Chemotaxicell-24 installed in each well at 1 × 106 cells /well. Likewise, parental L1.2 cells for these transfectants were prepared and added to the Chemotaxicell-24. Cell migration was allowed for 2 h at 37°C in a 5% CO2 atmosphere. The cells that migrated to the lower well were lysed and quantified using a PicoGreen double-stranded DNA quantification reagent. The data are expressed as the mean±SE of the triplicate results. (Reproduced from Okada et al. [40]).
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC2279154&req=5

Fig1: Chemoattraction activity for cells expressing specific receptors in vitro induced by transfection of Ad-RGD-chemokines into A549 cells. Chemoattractant activity of culture supernatants of A549 cells transfected with each chemokine gene-carrying Ad-RGD against the stable specific chemokine receptor-expressing cells. The culture supernatants of intact A549 cells, Ad-RGD-Luc-transfected A549 (Luc/A549) cells, and chemokine gene-transduced A549 cells were prepared and diluted with the assay medium. The fractional values within the parentheses in each panel express the dilution factor. These samples and recombinant chemokines dissolved with the assay medium were added to a 24-well culture plate. Cells expressing specific receptors for CCL17 and CCL22 (L1.2/CCR4), CCL20 (L1.2/CCR6), CCL19 and CCL21 (L1.2/CCR7), CCL27 (L1.2/CCR10), XCL1 (L1.2/XCR1), or CX3CL1 (L1.2/CX3CR1) were suspended with the assay medium and placed in a Chemotaxicell-24 installed in each well at 1 × 106 cells /well. Likewise, parental L1.2 cells for these transfectants were prepared and added to the Chemotaxicell-24. Cell migration was allowed for 2 h at 37°C in a 5% CO2 atmosphere. The cells that migrated to the lower well were lysed and quantified using a PicoGreen double-stranded DNA quantification reagent. The data are expressed as the mean±SE of the triplicate results. (Reproduced from Okada et al. [40]).

Mentions: For evaluating tumor-suppressive effect of chemokines, eight chemokines were encoded in recombinant Ad-RGD vectors and chemoattraction activity for cells expressing specific receptors CCL17 and CCL22 (L1.2/CCR4), CCL20 (L1.2/CCR6), CCL19 and CCL21 (L1.2/CCR7), CCL27 (L1.2/CCR10), XCL1 (L1.2/XCR1), or CX3CL1 (L1.2/CX3CR1) in vitro induced by tranfection of Ad-RGD-chemokines into A549 cells was investigated. The results demonstrated the chemotactic activity for specific receptor-expressing cells (Fig. 1) (40). In another study, OV-HM ovarian carcinoma was used as a model and the antitumor effect of chemokines was investigated. Of the evaluated chemokines, ILC/CCL27 had a significant antitumor effect, and both CCL27 and CX3CL1 induced the accumulation of CD3+ T cells and NK cells in the tumor upon transfection into tumor cells through the Ad-RGD vector (Fig. 2). Additional experiments demonstrated that the antitumor activity is T cell-dependent and both CD4+ and CD8+ are involved in the response (39).Fig. 1


Immune cell recruitment and cell-based system for cancer therapy.

Gao JQ, Okada N, Mayumi T, Nakagawa S - Pharm. Res. (2007)

Chemoattraction activity for cells expressing specific receptors in vitro induced by transfection of Ad-RGD-chemokines into A549 cells. Chemoattractant activity of culture supernatants of A549 cells transfected with each chemokine gene-carrying Ad-RGD against the stable specific chemokine receptor-expressing cells. The culture supernatants of intact A549 cells, Ad-RGD-Luc-transfected A549 (Luc/A549) cells, and chemokine gene-transduced A549 cells were prepared and diluted with the assay medium. The fractional values within the parentheses in each panel express the dilution factor. These samples and recombinant chemokines dissolved with the assay medium were added to a 24-well culture plate. Cells expressing specific receptors for CCL17 and CCL22 (L1.2/CCR4), CCL20 (L1.2/CCR6), CCL19 and CCL21 (L1.2/CCR7), CCL27 (L1.2/CCR10), XCL1 (L1.2/XCR1), or CX3CL1 (L1.2/CX3CR1) were suspended with the assay medium and placed in a Chemotaxicell-24 installed in each well at 1 × 106 cells /well. Likewise, parental L1.2 cells for these transfectants were prepared and added to the Chemotaxicell-24. Cell migration was allowed for 2 h at 37°C in a 5% CO2 atmosphere. The cells that migrated to the lower well were lysed and quantified using a PicoGreen double-stranded DNA quantification reagent. The data are expressed as the mean±SE of the triplicate results. (Reproduced from Okada et al. [40]).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2279154&req=5

Fig1: Chemoattraction activity for cells expressing specific receptors in vitro induced by transfection of Ad-RGD-chemokines into A549 cells. Chemoattractant activity of culture supernatants of A549 cells transfected with each chemokine gene-carrying Ad-RGD against the stable specific chemokine receptor-expressing cells. The culture supernatants of intact A549 cells, Ad-RGD-Luc-transfected A549 (Luc/A549) cells, and chemokine gene-transduced A549 cells were prepared and diluted with the assay medium. The fractional values within the parentheses in each panel express the dilution factor. These samples and recombinant chemokines dissolved with the assay medium were added to a 24-well culture plate. Cells expressing specific receptors for CCL17 and CCL22 (L1.2/CCR4), CCL20 (L1.2/CCR6), CCL19 and CCL21 (L1.2/CCR7), CCL27 (L1.2/CCR10), XCL1 (L1.2/XCR1), or CX3CL1 (L1.2/CX3CR1) were suspended with the assay medium and placed in a Chemotaxicell-24 installed in each well at 1 × 106 cells /well. Likewise, parental L1.2 cells for these transfectants were prepared and added to the Chemotaxicell-24. Cell migration was allowed for 2 h at 37°C in a 5% CO2 atmosphere. The cells that migrated to the lower well were lysed and quantified using a PicoGreen double-stranded DNA quantification reagent. The data are expressed as the mean±SE of the triplicate results. (Reproduced from Okada et al. [40]).
Mentions: For evaluating tumor-suppressive effect of chemokines, eight chemokines were encoded in recombinant Ad-RGD vectors and chemoattraction activity for cells expressing specific receptors CCL17 and CCL22 (L1.2/CCR4), CCL20 (L1.2/CCR6), CCL19 and CCL21 (L1.2/CCR7), CCL27 (L1.2/CCR10), XCL1 (L1.2/XCR1), or CX3CL1 (L1.2/CX3CR1) in vitro induced by tranfection of Ad-RGD-chemokines into A549 cells was investigated. The results demonstrated the chemotactic activity for specific receptor-expressing cells (Fig. 1) (40). In another study, OV-HM ovarian carcinoma was used as a model and the antitumor effect of chemokines was investigated. Of the evaluated chemokines, ILC/CCL27 had a significant antitumor effect, and both CCL27 and CX3CL1 induced the accumulation of CD3+ T cells and NK cells in the tumor upon transfection into tumor cells through the Ad-RGD vector (Fig. 2). Additional experiments demonstrated that the antitumor activity is T cell-dependent and both CD4+ and CD8+ are involved in the response (39).Fig. 1

Bottom Line: Immune cells, such as cytotoxic T lymphocytes, natural killer cells, B cells, and dendritic cells, have a central role in cancer immunotherapy.It is well established that the basis and premise of immunotherapy is the accumulation of effective immune cells in tumor tissues.Recent characterization of various chemokines and chemokine receptors in the immune system has increased our knowledge of the regulatory mechanisms of the immune response and tolerance based on immune cell localization.

View Article: PubMed Central - PubMed

Affiliation: College of Pharmaceutical Sciences, Zhejiang University, 388 Yuhangtang Road, Hangzhou 310058, People's Republic of China. gaojianqing1029@yahoo.com.cn

ABSTRACT
Immune cells, such as cytotoxic T lymphocytes, natural killer cells, B cells, and dendritic cells, have a central role in cancer immunotherapy. Conventional studies of cancer immunotherapy have focused mainly on the search for an efficient means to prime/activate tumor-associated antigen-specific immunity. A systematic understanding of the molecular basis of the trafficking and biodistribution of immune cells, however, is important for the development of more efficacious cancer immunotherapies. It is well established that the basis and premise of immunotherapy is the accumulation of effective immune cells in tumor tissues. Therefore, it is crucial to control the distribution of immune cells to optimize cancer immunotherapy. Recent characterization of various chemokines and chemokine receptors in the immune system has increased our knowledge of the regulatory mechanisms of the immune response and tolerance based on immune cell localization. Here, we review the immune cell recruitment and cell-based systems that can potentially control the systemic pharmacokinetics of immune cells and, in particular, focus on cell migrating molecules, i.e., chemokines, and their receptors, and their use in cancer immunotherapy.

Show MeSH
Related in: MedlinePlus