9 Citations (Scopus)

Abstract

Mantle cell lymphoma (MCL) is a B cell malignancy that is resistant to conventional therapies. High-dose therapy (HDT) followed by stem cell transplantation is effective in inducing remission. However, residual lymphoma cells are eventually responsible for the subsequent relapse. Effective therapeutic strategies to eliminate the residual lymphoma is required. In this study, we have examined the in vitro and in vivo anti-lymphoma effects of MCL-specific cytotoxic T lymphocytes (CTLs) that were generated using dendritic cells (DCs) fused with MCL cells for immunostimulation. Dendritic cells were generated in vitro using dendritic cell-specific medium, cytomorphology, immunophenotypes and functional capabilities of the generated DCs were studied. Such DCs were then used for the preparation of DC-MCL hybrids and the DC-MCL hybrids were used to generate CTLs against MCL cells and tested for their MCL-specific cytotoxicity in vitro and in vivo. The CTLs demonstrated MCL-specific cytotoxicity in vitro against GRANT-519, a human MCL cell line. These CTLs did not show significant effect against an irrelevant target. To test the in vivo therapeutic effect of DC-MCL hybrid-stimulated CTLs, a preclinical model consisting of NOD-SCID mice bearing Granta 519 was developed. The NOD-SCID mice bearing Granta-519 MCL tumors were treated with DC-MCL hybrids and the same donor T lymphocytes. There was an increase in survival (60% in mice treated with DC-MCL hybrid approach compared to 20% in the untreated group). Histological analysis of liver from control and treated mice displayed a decrease in the number of the tumor nodules in the treatment group. These results indicate the potential of DC-based therapy for the treatment of MCL.

Original languageEnglish (US)
Pages (from-to)1337-1343
Number of pages7
JournalInternational journal of oncology
Volume28
Issue number6
StatePublished - Jun 1 2006

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Mantle-Cell Lymphoma
Cell- and Tissue-Based Therapy
Dendritic Cells
Cytotoxic T-Lymphocytes
Lymphoma
Inbred NOD Mouse
SCID Mice
Therapeutics
Neoplasms
Hybrid Cells
Stem Cell Transplantation
Therapeutic Uses

Keywords

  • Antigen priming
  • Cytotoxic T lymphocytes
  • Dendritic cells
  • Mantle cell lymphoma

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Dendritic cell-based therapy for mantle cell lymphoma. / Munger, Corey M.; Vose, Julie Marie; Joshi, Shantaram S.

In: International journal of oncology, Vol. 28, No. 6, 01.06.2006, p. 1337-1343.

Research output: Contribution to journalArticle

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abstract = "Mantle cell lymphoma (MCL) is a B cell malignancy that is resistant to conventional therapies. High-dose therapy (HDT) followed by stem cell transplantation is effective in inducing remission. However, residual lymphoma cells are eventually responsible for the subsequent relapse. Effective therapeutic strategies to eliminate the residual lymphoma is required. In this study, we have examined the in vitro and in vivo anti-lymphoma effects of MCL-specific cytotoxic T lymphocytes (CTLs) that were generated using dendritic cells (DCs) fused with MCL cells for immunostimulation. Dendritic cells were generated in vitro using dendritic cell-specific medium, cytomorphology, immunophenotypes and functional capabilities of the generated DCs were studied. Such DCs were then used for the preparation of DC-MCL hybrids and the DC-MCL hybrids were used to generate CTLs against MCL cells and tested for their MCL-specific cytotoxicity in vitro and in vivo. The CTLs demonstrated MCL-specific cytotoxicity in vitro against GRANT-519, a human MCL cell line. These CTLs did not show significant effect against an irrelevant target. To test the in vivo therapeutic effect of DC-MCL hybrid-stimulated CTLs, a preclinical model consisting of NOD-SCID mice bearing Granta 519 was developed. The NOD-SCID mice bearing Granta-519 MCL tumors were treated with DC-MCL hybrids and the same donor T lymphocytes. There was an increase in survival (60{\%} in mice treated with DC-MCL hybrid approach compared to 20{\%} in the untreated group). Histological analysis of liver from control and treated mice displayed a decrease in the number of the tumor nodules in the treatment group. These results indicate the potential of DC-based therapy for the treatment of MCL.",
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T1 - Dendritic cell-based therapy for mantle cell lymphoma

AU - Munger, Corey M.

AU - Vose, Julie Marie

AU - Joshi, Shantaram S

PY - 2006/6/1

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N2 - Mantle cell lymphoma (MCL) is a B cell malignancy that is resistant to conventional therapies. High-dose therapy (HDT) followed by stem cell transplantation is effective in inducing remission. However, residual lymphoma cells are eventually responsible for the subsequent relapse. Effective therapeutic strategies to eliminate the residual lymphoma is required. In this study, we have examined the in vitro and in vivo anti-lymphoma effects of MCL-specific cytotoxic T lymphocytes (CTLs) that were generated using dendritic cells (DCs) fused with MCL cells for immunostimulation. Dendritic cells were generated in vitro using dendritic cell-specific medium, cytomorphology, immunophenotypes and functional capabilities of the generated DCs were studied. Such DCs were then used for the preparation of DC-MCL hybrids and the DC-MCL hybrids were used to generate CTLs against MCL cells and tested for their MCL-specific cytotoxicity in vitro and in vivo. The CTLs demonstrated MCL-specific cytotoxicity in vitro against GRANT-519, a human MCL cell line. These CTLs did not show significant effect against an irrelevant target. To test the in vivo therapeutic effect of DC-MCL hybrid-stimulated CTLs, a preclinical model consisting of NOD-SCID mice bearing Granta 519 was developed. The NOD-SCID mice bearing Granta-519 MCL tumors were treated with DC-MCL hybrids and the same donor T lymphocytes. There was an increase in survival (60% in mice treated with DC-MCL hybrid approach compared to 20% in the untreated group). Histological analysis of liver from control and treated mice displayed a decrease in the number of the tumor nodules in the treatment group. These results indicate the potential of DC-based therapy for the treatment of MCL.

AB - Mantle cell lymphoma (MCL) is a B cell malignancy that is resistant to conventional therapies. High-dose therapy (HDT) followed by stem cell transplantation is effective in inducing remission. However, residual lymphoma cells are eventually responsible for the subsequent relapse. Effective therapeutic strategies to eliminate the residual lymphoma is required. In this study, we have examined the in vitro and in vivo anti-lymphoma effects of MCL-specific cytotoxic T lymphocytes (CTLs) that were generated using dendritic cells (DCs) fused with MCL cells for immunostimulation. Dendritic cells were generated in vitro using dendritic cell-specific medium, cytomorphology, immunophenotypes and functional capabilities of the generated DCs were studied. Such DCs were then used for the preparation of DC-MCL hybrids and the DC-MCL hybrids were used to generate CTLs against MCL cells and tested for their MCL-specific cytotoxicity in vitro and in vivo. The CTLs demonstrated MCL-specific cytotoxicity in vitro against GRANT-519, a human MCL cell line. These CTLs did not show significant effect against an irrelevant target. To test the in vivo therapeutic effect of DC-MCL hybrid-stimulated CTLs, a preclinical model consisting of NOD-SCID mice bearing Granta 519 was developed. The NOD-SCID mice bearing Granta-519 MCL tumors were treated with DC-MCL hybrids and the same donor T lymphocytes. There was an increase in survival (60% in mice treated with DC-MCL hybrid approach compared to 20% in the untreated group). Histological analysis of liver from control and treated mice displayed a decrease in the number of the tumor nodules in the treatment group. These results indicate the potential of DC-based therapy for the treatment of MCL.

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