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Autologous lymphoma vaccines induce human T cell responses against multiple, unique epitopes
Sivasubramanian Baskar, … , Carol B. Kobrin, Larry W. Kwak
Sivasubramanian Baskar, … , Carol B. Kobrin, Larry W. Kwak
Published May 15, 2004
Citation Information: J Clin Invest. 2004;113(10):1498-1510. https://doi.org/10.1172/JCI20312.
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Article Oncology

Autologous lymphoma vaccines induce human T cell responses against multiple, unique epitopes

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Abstract

The clonotypic surface Ig receptor expressed by malignant B cells, idiotype, is a tumor-specific antigen and an attractive target for active immunotherapy. While Ab’s specific for tumor idiotype have been well described in patients with B cell malignancies, the precise antigenic epitopes in human idiotype recognized by autologous T cells remain largely unknown. We report here that T cell lines generated from lymphoma patients actively immunized with idiotype protein specifically recognized multiple, unique immunodominant epitopes in autologous tumor idiotype. Synthetic peptides corresponding to hypervariable, but not framework, regions of Ig heavy chain specifically stimulated CD4+ and CD8+ T cells to proliferate and secrete proinflammatory cytokines in an MHC-associated manner. Detailed analysis revealed a minimal determinant of an immunodominant epitope, comprising critical residues at the amino terminus that may be a product of somatic hypermutation. Association of idiotype-specific T cell responses with previously documented molecular remissions in idiotype-vaccinated patients suggests that the newly identified T cell epitopes may be clinically relevant. Such antigenic epitopes may serve as candidates for novel peptide-vaccine strategies, and as tools to selectively expand tumor antigen–specific T cells for adoptive immunotherapy and for monitoring T cell immunity in vaccinated patients.

Authors

Sivasubramanian Baskar, Carol B. Kobrin, Larry W. Kwak

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Figure 4

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Cytokine response by T cells to peptides derived from CDRs of Ig VH. T c...
Cytokine response by T cells to peptides derived from CDRs of Ig VH. T cells from three additional patients, TL (A), BS (B), and BL (C), were cultured with irradiated autologous PBMCs in the absence or presence of 50 ∝M autologous CDR or FWR peptides (Table 3). GM-CSF responses from a representative experiment are shown. Similar results were obtained at lower antigen doses with BS and BL T cell lines (data not shown).

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ISSN: 0021-9738 (print), 1558-8238 (online)

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