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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.

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Accumulation of immune cells in ovarian carcinoma in vivo by transfection of chemokine-encoding adenovirus vectors. Left: CD3-positive lymphocytes infiltrated into OV-HM tumors infected with Ad-RGD-mCCL27 and Ad-RGD-mCX3CL1. a–d Representative immunohistochemical appearance of tumor nodules from mice inoculated intradermally with 1 × 106 OV-HM cells infected with a none, b Ad-RGD, c Ad-RGD-mCCL27, or d Ad-RGD-mCX3CL1. Right: NK cells infiltrated into OV-HM tumors infected with Ad-RGD-mCCL27 and Ad-RGD-mCX3CL1. e–h Representative immunohistochemical appearance of tumor nodules from mice inoculated intradermally with 1 × 106 OV-HM cells infected with e none, f Ad-RGD, g Ad-RGD-mCCL27, or h Ad-RGD-mCX3CL1. (Reproduced from Gao et al. [39]).
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Fig2: Accumulation of immune cells in ovarian carcinoma in vivo by transfection of chemokine-encoding adenovirus vectors. Left: CD3-positive lymphocytes infiltrated into OV-HM tumors infected with Ad-RGD-mCCL27 and Ad-RGD-mCX3CL1. a–d Representative immunohistochemical appearance of tumor nodules from mice inoculated intradermally with 1 × 106 OV-HM cells infected with a none, b Ad-RGD, c Ad-RGD-mCCL27, or d Ad-RGD-mCX3CL1. Right: NK cells infiltrated into OV-HM tumors infected with Ad-RGD-mCCL27 and Ad-RGD-mCX3CL1. e–h Representative immunohistochemical appearance of tumor nodules from mice inoculated intradermally with 1 × 106 OV-HM cells infected with e none, f Ad-RGD, g Ad-RGD-mCCL27, or h Ad-RGD-mCX3CL1. (Reproduced from Gao et al. [39]).

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)

Accumulation of immune cells in ovarian carcinoma in vivo by transfection of chemokine-encoding adenovirus vectors. Left: CD3-positive lymphocytes infiltrated into OV-HM tumors infected with Ad-RGD-mCCL27 and Ad-RGD-mCX3CL1. a–d Representative immunohistochemical appearance of tumor nodules from mice inoculated intradermally with 1 × 106 OV-HM cells infected with a none, b Ad-RGD, c Ad-RGD-mCCL27, or d Ad-RGD-mCX3CL1. Right: NK cells infiltrated into OV-HM tumors infected with Ad-RGD-mCCL27 and Ad-RGD-mCX3CL1. e–h Representative immunohistochemical appearance of tumor nodules from mice inoculated intradermally with 1 × 106 OV-HM cells infected with e none, f Ad-RGD, g Ad-RGD-mCCL27, or h Ad-RGD-mCX3CL1. (Reproduced from Gao et al. [39]).
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Related In: Results  -  Collection

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Fig2: Accumulation of immune cells in ovarian carcinoma in vivo by transfection of chemokine-encoding adenovirus vectors. Left: CD3-positive lymphocytes infiltrated into OV-HM tumors infected with Ad-RGD-mCCL27 and Ad-RGD-mCX3CL1. a–d Representative immunohistochemical appearance of tumor nodules from mice inoculated intradermally with 1 × 106 OV-HM cells infected with a none, b Ad-RGD, c Ad-RGD-mCCL27, or d Ad-RGD-mCX3CL1. Right: NK cells infiltrated into OV-HM tumors infected with Ad-RGD-mCCL27 and Ad-RGD-mCX3CL1. e–h Representative immunohistochemical appearance of tumor nodules from mice inoculated intradermally with 1 × 106 OV-HM cells infected with e none, f Ad-RGD, g Ad-RGD-mCCL27, or h Ad-RGD-mCX3CL1. (Reproduced from Gao et al. [39]).
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