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Expansion of melanoma-specific cytolytic CD8+ T cell precursors in patients with metastatic melanoma vaccinated with CD34+ progenitor-derived dendritic cells.

Paczesny S, Banchereau J, Wittkowski KM, Saracino G, Fay J, Palucka AK - J. Exp. Med. (2004)

Bottom Line: Cancer vaccines aim at inducing (a) tumor-specific effector T cells able to reduce/eliminate the tumor mass, and (b) long-lasting tumor-specific memory T cells able to control tumor relapse.Thus, CD34-DC vaccines can expand melanoma-specific CTL precursors that can kill melanoma antigen-expressing targets.These results justify the design of larger follow-up studies to assess the immunological and clinical response to peptide-pulsed CD34-DC vaccines.

View Article: PubMed Central - PubMed

Affiliation: Baylor Institute for Immunology Research, Dallas, TX 75204, USA.

ABSTRACT
Cancer vaccines aim at inducing (a) tumor-specific effector T cells able to reduce/eliminate the tumor mass, and (b) long-lasting tumor-specific memory T cells able to control tumor relapse. We have shown earlier, in 18 human histocompatibility leukocyte antigen (HLA)-A*0201 patients with metastatic melanoma, that vaccination with peptide-loaded CD34-dendritic cells (DCs) leads to expansion of melanoma-specific interferon gamma-producing CD8+ T cells in the blood. Here, we show in 9 out of 12 analyzed patients the expansion of cytolytic CD8+ T cell precursors specific for melanoma differentiation antigens. These precursors yield, upon single restimulation with melanoma peptide-pulsed DCs, cytotoxic T lymphocytes (CTLs) able to kill melanoma cells. Melanoma-specific CTLs can be grown in vitro and can be detected in three assays: (a) melanoma tetramer binding, (b) killing of melanoma peptide-pulsed T2 cells, and (c) killing of HLA-A*0201 melanoma cells. The cytolytic activity of expanded CTLs correlates with the frequency of melanoma tetramer binding CD8+ T cells. Thus, CD34-DC vaccines can expand melanoma-specific CTL precursors that can kill melanoma antigen-expressing targets. These results justify the design of larger follow-up studies to assess the immunological and clinical response to peptide-pulsed CD34-DC vaccines.

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CTL activity against allogenic tumor cell lines before and after vaccination. Killing of Me275 melanoma cells, and of control MCF7 breast cancer and K562 cells, by cultured CD8+ T cells from all patients tested at baseline (Pre) and after fourth DC vaccine (Post). Ordinate, nonsubtracted specific lysis at the E/T ratio of 30–25:1; abscissa, patient number (see Table I). Average of all experiments for each patient (see Table S1) is shown. Prevaccination PBMCs were analyzed only once due to the limited availability of cells. Wilcoxon paired test.
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fig3: CTL activity against allogenic tumor cell lines before and after vaccination. Killing of Me275 melanoma cells, and of control MCF7 breast cancer and K562 cells, by cultured CD8+ T cells from all patients tested at baseline (Pre) and after fourth DC vaccine (Post). Ordinate, nonsubtracted specific lysis at the E/T ratio of 30–25:1; abscissa, patient number (see Table I). Average of all experiments for each patient (see Table S1) is shown. Prevaccination PBMCs were analyzed only once due to the limited availability of cells. Wilcoxon paired test.

Mentions: The capacity of cultured CD8+ T cells from post-DC vaccination blood to kill melanoma cell lines was then analyzed in 12 patients (Fig. 3 and Table S1). The median-specific lysis of Me275 cells was 12% (range: 0–39). The lysis of control MCF7 and K562 cells was 8 (range: 0–17) and 9% (range: 0–46), respectively. Independent experiments measuring CD8+ T cells from the same patient yielded reproducible results (Table S1). No induction of CTL activity against Me275 melanoma cells could be found when CD8+ T cells from three healthy HLA-A*0201 volunteers were used (median 2%).


Expansion of melanoma-specific cytolytic CD8+ T cell precursors in patients with metastatic melanoma vaccinated with CD34+ progenitor-derived dendritic cells.

Paczesny S, Banchereau J, Wittkowski KM, Saracino G, Fay J, Palucka AK - J. Exp. Med. (2004)

CTL activity against allogenic tumor cell lines before and after vaccination. Killing of Me275 melanoma cells, and of control MCF7 breast cancer and K562 cells, by cultured CD8+ T cells from all patients tested at baseline (Pre) and after fourth DC vaccine (Post). Ordinate, nonsubtracted specific lysis at the E/T ratio of 30–25:1; abscissa, patient number (see Table I). Average of all experiments for each patient (see Table S1) is shown. Prevaccination PBMCs were analyzed only once due to the limited availability of cells. Wilcoxon paired test.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2211788&req=5

fig3: CTL activity against allogenic tumor cell lines before and after vaccination. Killing of Me275 melanoma cells, and of control MCF7 breast cancer and K562 cells, by cultured CD8+ T cells from all patients tested at baseline (Pre) and after fourth DC vaccine (Post). Ordinate, nonsubtracted specific lysis at the E/T ratio of 30–25:1; abscissa, patient number (see Table I). Average of all experiments for each patient (see Table S1) is shown. Prevaccination PBMCs were analyzed only once due to the limited availability of cells. Wilcoxon paired test.
Mentions: The capacity of cultured CD8+ T cells from post-DC vaccination blood to kill melanoma cell lines was then analyzed in 12 patients (Fig. 3 and Table S1). The median-specific lysis of Me275 cells was 12% (range: 0–39). The lysis of control MCF7 and K562 cells was 8 (range: 0–17) and 9% (range: 0–46), respectively. Independent experiments measuring CD8+ T cells from the same patient yielded reproducible results (Table S1). No induction of CTL activity against Me275 melanoma cells could be found when CD8+ T cells from three healthy HLA-A*0201 volunteers were used (median 2%).

Bottom Line: Cancer vaccines aim at inducing (a) tumor-specific effector T cells able to reduce/eliminate the tumor mass, and (b) long-lasting tumor-specific memory T cells able to control tumor relapse.Thus, CD34-DC vaccines can expand melanoma-specific CTL precursors that can kill melanoma antigen-expressing targets.These results justify the design of larger follow-up studies to assess the immunological and clinical response to peptide-pulsed CD34-DC vaccines.

View Article: PubMed Central - PubMed

Affiliation: Baylor Institute for Immunology Research, Dallas, TX 75204, USA.

ABSTRACT
Cancer vaccines aim at inducing (a) tumor-specific effector T cells able to reduce/eliminate the tumor mass, and (b) long-lasting tumor-specific memory T cells able to control tumor relapse. We have shown earlier, in 18 human histocompatibility leukocyte antigen (HLA)-A*0201 patients with metastatic melanoma, that vaccination with peptide-loaded CD34-dendritic cells (DCs) leads to expansion of melanoma-specific interferon gamma-producing CD8+ T cells in the blood. Here, we show in 9 out of 12 analyzed patients the expansion of cytolytic CD8+ T cell precursors specific for melanoma differentiation antigens. These precursors yield, upon single restimulation with melanoma peptide-pulsed DCs, cytotoxic T lymphocytes (CTLs) able to kill melanoma cells. Melanoma-specific CTLs can be grown in vitro and can be detected in three assays: (a) melanoma tetramer binding, (b) killing of melanoma peptide-pulsed T2 cells, and (c) killing of HLA-A*0201 melanoma cells. The cytolytic activity of expanded CTLs correlates with the frequency of melanoma tetramer binding CD8+ T cells. Thus, CD34-DC vaccines can expand melanoma-specific CTL precursors that can kill melanoma antigen-expressing targets. These results justify the design of larger follow-up studies to assess the immunological and clinical response to peptide-pulsed CD34-DC vaccines.

Show MeSH
Related in: MedlinePlus