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Tumor lysate–specific cytotoxic T lymphocytes in multiple myeloma: promising effector cells for immunotherapy
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| Zeitschriftentitel: | Blood |
|---|---|
| Personen und Körperschaften: | , , , , |
| In: | Blood, 99, 2002, 9, S. 3280-3285 |
| Format: | E-Article |
| Sprache: | Englisch |
| veröffentlicht: |
American Society of Hematology
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| Schlagwörter: |
| author_facet |
Wen, Yue-Jin Min, Rui Tricot, Guido Barlogie, Bart Yi, Qing Wen, Yue-Jin Min, Rui Tricot, Guido Barlogie, Bart Yi, Qing |
|---|---|
| author |
Wen, Yue-Jin Min, Rui Tricot, Guido Barlogie, Bart Yi, Qing |
| spellingShingle |
Wen, Yue-Jin Min, Rui Tricot, Guido Barlogie, Bart Yi, Qing Blood Tumor lysate–specific cytotoxic T lymphocytes in multiple myeloma: promising effector cells for immunotherapy Cell Biology Hematology Immunology Biochemistry |
| author_sort |
wen, yue-jin |
| spelling |
Wen, Yue-Jin Min, Rui Tricot, Guido Barlogie, Bart Yi, Qing 1528-0020 0006-4971 American Society of Hematology Cell Biology Hematology Immunology Biochemistry http://dx.doi.org/10.1182/blood.v99.9.3280 <jats:title>Abstract</jats:title><jats:p>The idiotype protein, secreted by myeloma plasma cells, is a tumor-specific but weak antigen. Idiotype-based immunotherapy has been explored in myeloma patients with disappointing results. It is conceivable that myeloma cells contain a multitude of tumor antigens that can more effectively stimulate antitumor T cells. To explore the possibility of using whole myeloma cells as a source of tumor antigens for immunotherapy, the current study was undertaken to generate and examine the function of myeloma-specific cytotoxic T lymphocytes (CTLs) by using dendritic cells (DCs) pulsed with myeloma cell lysates as stimulating cells. After repeated stimulation, specific CTL lines, containing CD4+ and CD8+ T cells, were generated from myeloma patients. Our results show that these T cells not only recognized and lysed autologous myeloma protein–pulsed DCs, they also killed autologous primary myeloma cells. Occasionally, CTLs responded to autologous idiotype–pulsed DCs and to allogeneic primary myeloma cells. No cytolytic activity, however, was detected against autologous lymphocytes including B cells, suggesting that the T cells acted specifically against myeloma cells. Cytotoxicity against target cells was major histocompatibility complex class 1 and, to a lesser extent, class 2 restricted and was dependent mainly on the perforin-mediated pathway. CTLs secreted predominantly interferon-γ and tumor necrosis factor-α on antigenic stimulation, indicating a type 1 T-cell subset. These findings represent the first demonstration that tumor cell lysate–primed CTLs kill only myeloma cells, not autologous lymphocytes. This provides a rationale for myeloma cell–based immunotherapy in multiple myeloma.</jats:p> Tumor lysate–specific cytotoxic T lymphocytes in multiple myeloma: promising effector cells for immunotherapy Blood |
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American Society of Hematology, 2002 |
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| title |
Tumor lysate–specific cytotoxic T lymphocytes in multiple myeloma: promising effector cells for immunotherapy |
| title_unstemmed |
Tumor lysate–specific cytotoxic T lymphocytes in multiple myeloma: promising effector cells for immunotherapy |
| title_full |
Tumor lysate–specific cytotoxic T lymphocytes in multiple myeloma: promising effector cells for immunotherapy |
| title_fullStr |
Tumor lysate–specific cytotoxic T lymphocytes in multiple myeloma: promising effector cells for immunotherapy |
| title_full_unstemmed |
Tumor lysate–specific cytotoxic T lymphocytes in multiple myeloma: promising effector cells for immunotherapy |
| title_short |
Tumor lysate–specific cytotoxic T lymphocytes in multiple myeloma: promising effector cells for immunotherapy |
| title_sort |
tumor lysate–specific cytotoxic t lymphocytes in multiple myeloma: promising effector cells for immunotherapy |
| topic |
Cell Biology Hematology Immunology Biochemistry |
| url |
http://dx.doi.org/10.1182/blood.v99.9.3280 |
| publishDate |
2002 |
| physical |
3280-3285 |
| description |
<jats:title>Abstract</jats:title><jats:p>The idiotype protein, secreted by myeloma plasma cells, is a tumor-specific but weak antigen. Idiotype-based immunotherapy has been explored in myeloma patients with disappointing results. It is conceivable that myeloma cells contain a multitude of tumor antigens that can more effectively stimulate antitumor T cells. To explore the possibility of using whole myeloma cells as a source of tumor antigens for immunotherapy, the current study was undertaken to generate and examine the function of myeloma-specific cytotoxic T lymphocytes (CTLs) by using dendritic cells (DCs) pulsed with myeloma cell lysates as stimulating cells. After repeated stimulation, specific CTL lines, containing CD4+ and CD8+ T cells, were generated from myeloma patients. Our results show that these T cells not only recognized and lysed autologous myeloma protein–pulsed DCs, they also killed autologous primary myeloma cells. Occasionally, CTLs responded to autologous idiotype–pulsed DCs and to allogeneic primary myeloma cells. No cytolytic activity, however, was detected against autologous lymphocytes including B cells, suggesting that the T cells acted specifically against myeloma cells. Cytotoxicity against target cells was major histocompatibility complex class 1 and, to a lesser extent, class 2 restricted and was dependent mainly on the perforin-mediated pathway. CTLs secreted predominantly interferon-γ and tumor necrosis factor-α on antigenic stimulation, indicating a type 1 T-cell subset. These findings represent the first demonstration that tumor cell lysate–primed CTLs kill only myeloma cells, not autologous lymphocytes. This provides a rationale for myeloma cell–based immunotherapy in multiple myeloma.</jats:p> |
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| author | Wen, Yue-Jin, Min, Rui, Tricot, Guido, Barlogie, Bart, Yi, Qing |
| author_facet | Wen, Yue-Jin, Min, Rui, Tricot, Guido, Barlogie, Bart, Yi, Qing, Wen, Yue-Jin, Min, Rui, Tricot, Guido, Barlogie, Bart, Yi, Qing |
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| description | <jats:title>Abstract</jats:title><jats:p>The idiotype protein, secreted by myeloma plasma cells, is a tumor-specific but weak antigen. Idiotype-based immunotherapy has been explored in myeloma patients with disappointing results. It is conceivable that myeloma cells contain a multitude of tumor antigens that can more effectively stimulate antitumor T cells. To explore the possibility of using whole myeloma cells as a source of tumor antigens for immunotherapy, the current study was undertaken to generate and examine the function of myeloma-specific cytotoxic T lymphocytes (CTLs) by using dendritic cells (DCs) pulsed with myeloma cell lysates as stimulating cells. After repeated stimulation, specific CTL lines, containing CD4+ and CD8+ T cells, were generated from myeloma patients. Our results show that these T cells not only recognized and lysed autologous myeloma protein–pulsed DCs, they also killed autologous primary myeloma cells. Occasionally, CTLs responded to autologous idiotype–pulsed DCs and to allogeneic primary myeloma cells. No cytolytic activity, however, was detected against autologous lymphocytes including B cells, suggesting that the T cells acted specifically against myeloma cells. Cytotoxicity against target cells was major histocompatibility complex class 1 and, to a lesser extent, class 2 restricted and was dependent mainly on the perforin-mediated pathway. CTLs secreted predominantly interferon-γ and tumor necrosis factor-α on antigenic stimulation, indicating a type 1 T-cell subset. These findings represent the first demonstration that tumor cell lysate–primed CTLs kill only myeloma cells, not autologous lymphocytes. This provides a rationale for myeloma cell–based immunotherapy in multiple myeloma.</jats:p> |
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| imprint | American Society of Hematology, 2002 |
| imprint_str_mv | American Society of Hematology, 2002 |
| institution | DE-L229, DE-D275, DE-Bn3, DE-Brt1, DE-Zwi2, DE-D161, DE-Gla1, DE-Zi4, DE-15, DE-Pl11, DE-Rs1, DE-105, DE-14, DE-Ch1 |
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| spelling | Wen, Yue-Jin Min, Rui Tricot, Guido Barlogie, Bart Yi, Qing 1528-0020 0006-4971 American Society of Hematology Cell Biology Hematology Immunology Biochemistry http://dx.doi.org/10.1182/blood.v99.9.3280 <jats:title>Abstract</jats:title><jats:p>The idiotype protein, secreted by myeloma plasma cells, is a tumor-specific but weak antigen. Idiotype-based immunotherapy has been explored in myeloma patients with disappointing results. It is conceivable that myeloma cells contain a multitude of tumor antigens that can more effectively stimulate antitumor T cells. To explore the possibility of using whole myeloma cells as a source of tumor antigens for immunotherapy, the current study was undertaken to generate and examine the function of myeloma-specific cytotoxic T lymphocytes (CTLs) by using dendritic cells (DCs) pulsed with myeloma cell lysates as stimulating cells. After repeated stimulation, specific CTL lines, containing CD4+ and CD8+ T cells, were generated from myeloma patients. Our results show that these T cells not only recognized and lysed autologous myeloma protein–pulsed DCs, they also killed autologous primary myeloma cells. Occasionally, CTLs responded to autologous idiotype–pulsed DCs and to allogeneic primary myeloma cells. No cytolytic activity, however, was detected against autologous lymphocytes including B cells, suggesting that the T cells acted specifically against myeloma cells. Cytotoxicity against target cells was major histocompatibility complex class 1 and, to a lesser extent, class 2 restricted and was dependent mainly on the perforin-mediated pathway. CTLs secreted predominantly interferon-γ and tumor necrosis factor-α on antigenic stimulation, indicating a type 1 T-cell subset. These findings represent the first demonstration that tumor cell lysate–primed CTLs kill only myeloma cells, not autologous lymphocytes. This provides a rationale for myeloma cell–based immunotherapy in multiple myeloma.</jats:p> Tumor lysate–specific cytotoxic T lymphocytes in multiple myeloma: promising effector cells for immunotherapy Blood |
| spellingShingle | Wen, Yue-Jin, Min, Rui, Tricot, Guido, Barlogie, Bart, Yi, Qing, Blood, Tumor lysate–specific cytotoxic T lymphocytes in multiple myeloma: promising effector cells for immunotherapy, Cell Biology, Hematology, Immunology, Biochemistry |
| title | Tumor lysate–specific cytotoxic T lymphocytes in multiple myeloma: promising effector cells for immunotherapy |
| title_full | Tumor lysate–specific cytotoxic T lymphocytes in multiple myeloma: promising effector cells for immunotherapy |
| title_fullStr | Tumor lysate–specific cytotoxic T lymphocytes in multiple myeloma: promising effector cells for immunotherapy |
| title_full_unstemmed | Tumor lysate–specific cytotoxic T lymphocytes in multiple myeloma: promising effector cells for immunotherapy |
| title_short | Tumor lysate–specific cytotoxic T lymphocytes in multiple myeloma: promising effector cells for immunotherapy |
| title_sort | tumor lysate–specific cytotoxic t lymphocytes in multiple myeloma: promising effector cells for immunotherapy |
| title_unstemmed | Tumor lysate–specific cytotoxic T lymphocytes in multiple myeloma: promising effector cells for immunotherapy |
| topic | Cell Biology, Hematology, Immunology, Biochemistry |
| url | http://dx.doi.org/10.1182/blood.v99.9.3280 |