Autoreactive, Cytotoxic T Lymphocytes Specific for Peptides Derived from Normal B-Cell Differentiation Antigens in Healthy Individuals and Patients with B-Cell Malignancies

Matthias Grube, Katy Rezvani, Adrian Wiestner, Hiroshi Fujiwara, Giuseppe Sconocchia, Jan J. Melenhorst, Nancy Hensel, Gerald E. Marti, Larry W. Kwak, Wyndham Wilson, John A. Barrett

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Purpose: To investigate potential immunotherapeutic strategies in B lymphocytic malignancies we looked for CTLs recognizing CD19 and CD20 epitopes. Experimental Design: Three CD19 and CD20 peptides binding to HLA-A*0201 were identified and used to detect peptide specific CTLs by a quantitative real-time PCR to measure IFN-γ mRNA expression in 23 healthy individuals and 28 patients (18 chronic lymphocytic leukemia (CLL), 7 follicular lymphoma, 2 acute lymphocytic leukemia, and 1 large cell lymphoma). Peptide-specific CTLs were expanded in culture with CD40-activated B cells to test lytic activity in three patients. Results: In healthy individuals, CD8+ T-cell responses were detected in one to CD1974-82, in three to CD20 127-135, and three to CD20188-196. Seven of 27 patients (6 with CLL) had CD8+ T cells recognizing CD1974-82. Seven patients responded to CD20127-135 and three to CD20 188-196. All were CLL patients. CD1974-82-specific CTLs from three patients were expanded over 4 weeks. These cells were HLA-A*0201 specific and lytic for peptide-loaded antigen-presenting cells but not to malignant or unpulsed B cells. Conclusions: CTLs that recognize CD19 and CD20 epitopes exist in healthy individuals and may be increased in CLL patients. They are of low avidity and require high doses of peptide for activation. Strategies to increase T-cell avidity would be necessary for T-cell immunotherapeutic approaches using the peptides studied.

Original languageEnglish (US)
Pages (from-to)1047-1056
Number of pages10
JournalClinical Cancer Research
Volume10
Issue number3
DOIs
StatePublished - Feb 1 2004

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B-Lymphocyte Differentiation Antigens
Cytotoxic T-Lymphocytes
B-Lymphocytes
Peptides
B-Cell Chronic Lymphocytic Leukemia
Neoplasms
T-Lymphocytes
Epitopes
Follicular Lymphoma
Antigen-Presenting Cells
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Real-Time Polymerase Chain Reaction
Lymphoma
Research Design
Messenger RNA

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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Autoreactive, Cytotoxic T Lymphocytes Specific for Peptides Derived from Normal B-Cell Differentiation Antigens in Healthy Individuals and Patients with B-Cell Malignancies. / Grube, Matthias; Rezvani, Katy; Wiestner, Adrian; Fujiwara, Hiroshi; Sconocchia, Giuseppe; Melenhorst, Jan J.; Hensel, Nancy; Marti, Gerald E.; Kwak, Larry W.; Wilson, Wyndham; Barrett, John A.

In: Clinical Cancer Research, Vol. 10, No. 3, 01.02.2004, p. 1047-1056.

Research output: Contribution to journalArticle

Grube, Matthias ; Rezvani, Katy ; Wiestner, Adrian ; Fujiwara, Hiroshi ; Sconocchia, Giuseppe ; Melenhorst, Jan J. ; Hensel, Nancy ; Marti, Gerald E. ; Kwak, Larry W. ; Wilson, Wyndham ; Barrett, John A. / Autoreactive, Cytotoxic T Lymphocytes Specific for Peptides Derived from Normal B-Cell Differentiation Antigens in Healthy Individuals and Patients with B-Cell Malignancies. In: Clinical Cancer Research. 2004 ; Vol. 10, No. 3. pp. 1047-1056.
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abstract = "Purpose: To investigate potential immunotherapeutic strategies in B lymphocytic malignancies we looked for CTLs recognizing CD19 and CD20 epitopes. Experimental Design: Three CD19 and CD20 peptides binding to HLA-A*0201 were identified and used to detect peptide specific CTLs by a quantitative real-time PCR to measure IFN-γ mRNA expression in 23 healthy individuals and 28 patients (18 chronic lymphocytic leukemia (CLL), 7 follicular lymphoma, 2 acute lymphocytic leukemia, and 1 large cell lymphoma). Peptide-specific CTLs were expanded in culture with CD40-activated B cells to test lytic activity in three patients. Results: In healthy individuals, CD8+ T-cell responses were detected in one to CD1974-82, in three to CD20 127-135, and three to CD20188-196. Seven of 27 patients (6 with CLL) had CD8+ T cells recognizing CD1974-82. Seven patients responded to CD20127-135 and three to CD20 188-196. All were CLL patients. CD1974-82-specific CTLs from three patients were expanded over 4 weeks. These cells were HLA-A*0201 specific and lytic for peptide-loaded antigen-presenting cells but not to malignant or unpulsed B cells. Conclusions: CTLs that recognize CD19 and CD20 epitopes exist in healthy individuals and may be increased in CLL patients. They are of low avidity and require high doses of peptide for activation. Strategies to increase T-cell avidity would be necessary for T-cell immunotherapeutic approaches using the peptides studied.",
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T1 - Autoreactive, Cytotoxic T Lymphocytes Specific for Peptides Derived from Normal B-Cell Differentiation Antigens in Healthy Individuals and Patients with B-Cell Malignancies

AU - Grube, Matthias

AU - Rezvani, Katy

AU - Wiestner, Adrian

AU - Fujiwara, Hiroshi

AU - Sconocchia, Giuseppe

AU - Melenhorst, Jan J.

AU - Hensel, Nancy

AU - Marti, Gerald E.

AU - Kwak, Larry W.

AU - Wilson, Wyndham

AU - Barrett, John A.

PY - 2004/2/1

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N2 - Purpose: To investigate potential immunotherapeutic strategies in B lymphocytic malignancies we looked for CTLs recognizing CD19 and CD20 epitopes. Experimental Design: Three CD19 and CD20 peptides binding to HLA-A*0201 were identified and used to detect peptide specific CTLs by a quantitative real-time PCR to measure IFN-γ mRNA expression in 23 healthy individuals and 28 patients (18 chronic lymphocytic leukemia (CLL), 7 follicular lymphoma, 2 acute lymphocytic leukemia, and 1 large cell lymphoma). Peptide-specific CTLs were expanded in culture with CD40-activated B cells to test lytic activity in three patients. Results: In healthy individuals, CD8+ T-cell responses were detected in one to CD1974-82, in three to CD20 127-135, and three to CD20188-196. Seven of 27 patients (6 with CLL) had CD8+ T cells recognizing CD1974-82. Seven patients responded to CD20127-135 and three to CD20 188-196. All were CLL patients. CD1974-82-specific CTLs from three patients were expanded over 4 weeks. These cells were HLA-A*0201 specific and lytic for peptide-loaded antigen-presenting cells but not to malignant or unpulsed B cells. Conclusions: CTLs that recognize CD19 and CD20 epitopes exist in healthy individuals and may be increased in CLL patients. They are of low avidity and require high doses of peptide for activation. Strategies to increase T-cell avidity would be necessary for T-cell immunotherapeutic approaches using the peptides studied.

AB - Purpose: To investigate potential immunotherapeutic strategies in B lymphocytic malignancies we looked for CTLs recognizing CD19 and CD20 epitopes. Experimental Design: Three CD19 and CD20 peptides binding to HLA-A*0201 were identified and used to detect peptide specific CTLs by a quantitative real-time PCR to measure IFN-γ mRNA expression in 23 healthy individuals and 28 patients (18 chronic lymphocytic leukemia (CLL), 7 follicular lymphoma, 2 acute lymphocytic leukemia, and 1 large cell lymphoma). Peptide-specific CTLs were expanded in culture with CD40-activated B cells to test lytic activity in three patients. Results: In healthy individuals, CD8+ T-cell responses were detected in one to CD1974-82, in three to CD20 127-135, and three to CD20188-196. Seven of 27 patients (6 with CLL) had CD8+ T cells recognizing CD1974-82. Seven patients responded to CD20127-135 and three to CD20 188-196. All were CLL patients. CD1974-82-specific CTLs from three patients were expanded over 4 weeks. These cells were HLA-A*0201 specific and lytic for peptide-loaded antigen-presenting cells but not to malignant or unpulsed B cells. Conclusions: CTLs that recognize CD19 and CD20 epitopes exist in healthy individuals and may be increased in CLL patients. They are of low avidity and require high doses of peptide for activation. Strategies to increase T-cell avidity would be necessary for T-cell immunotherapeutic approaches using the peptides studied.

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