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Abstracts (complete list) - Wissenschaft Online

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Kathrin Hofer, Holger Kroenig, Heinke Conrad, Barbara Kast, Christian Peschel, Helga<br />

Bernhard<br />

Generation of Th1 lymphocyte clones against an<br />

immunodominant epitope of NY-ESO-1<br />

Since CD4+ T cells play a critical role in generating and maintaining antigen-specific<br />

cellular and humoral immune responses our current study focuses on the generation of<br />

T helper cells from healthy donors and multiple myeloma patients. Our approach is the<br />

isolation of high avidity tumor antigen specific class - II- restricted T cell receptors<br />

(TCRs) for an optimized T cell transfer strategy.<br />

The Cancer Testis (CT) antigen NY-ESO-1 is one of the most immunogenic cancer<br />

antigens eliciting strong humoral and cellular immune responses in tumor patients and<br />

is a promising candidate antigen for successful adoptive T cell transfer.<br />

We achieved to generate NY-ESO-1 specific T helper1 clones from HLA-DR1+ and HLA-<br />

DR4+ healthy donors by stimulation of CD4+ T cells with autologous dendritic cells (DC)<br />

pulsed with the NY-ESO-1 87-111 peptide known to be presented with HLA-DR1+ and<br />

HLA-DR4+. The specifity of CD4+ T helper cell clones was determined by proliferation<br />

assays and IFN gamma ELISPOT through screening with NY-ESO-187-111 peptide. By<br />

limiting dilution of the NY-ESO-1-specific T cell populations we succeeded to isolate T<br />

cell clones which recognized NY-ESO-1-pulsed target cells and DCs pulsed with NY-ESO-<br />

1 protein.<br />

The ability to isolate NY-ESO-1- specific T helper1 cells facilitates the development of T<br />

cell transfer regiments which are based on class-II-restricted TCR-transduced T cells for<br />

a treatment of patients with multiple myeloma.

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