A Polyvalent Cellular Vaccine Induces T-cell Responses Against Specific Self-antigens Overexpressed in Chronic Lymphocytic B-cell Leukemia

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A Polyvalent Cellular Vaccine Induces T-cell Responses Against Specific

Self-antigens Overexpressed in Chronic Lymphocytic B-cell Leukemia.

Konrad Kronenberger, Elfriede Noner, Bernhard enberger, Ulrich Wahl,

Dreyling, Hallek, and Ralph Mocikat

J Immunother, September 5, 2008; .

Helmholtz-Zentrum München, Deutsches Forschungszentrum für Gesundheit und

Umwelt, Institut für Molekulare Immunologie München daggerFresenius GmbH

Gräfelfing double daggerLudwig-Maximilians-Universität, III. Medizinische

Klinik, München section signUniversität zu Köln, I. Medizinische Klinik, Köln,

Germany.

B cell-derived chronic lymphocytic leukemia (CLL) is an incurable disease that

requires innovative therapeutic regimens. Experimental approaches of

immunotherapy aiming at induction of systemic T-cell responses have been

developed. Trioma cells provide a potent vaccine derived from malignant B cells

that allows multiple antigens (Ags) from the parental tumor to be ingested by

Ag-presenting cells. Like other strategies using modified whole tumor cells,

this approach induces polyvalent responses. Using trioma cell-pulsed dendritic

cells (DCs) for T-cell activation in vitro, we asked whether specific Ags

overexpressed by CLL can be identified as target structures of such responses

and what is the nature of these Ags. Expression levels of several genes in CLL

samples were quantitated by reverse transcriptase-polymerase chain reaction. T

lymphocytes were polyvalently stimulated by trioma-pulsed DCs and specificities

were tested by determining cytokine secretion in the presence of target cells

transfected with RNA coding for those Ags that were found to be overexpressed.

We demonstrate that DCs pulsed with the modified tumor cells efficiently

activate T lymphocytes against CLL and that overexpressed Ags related to

leukemogenesis, such as BCL-2, MDM2, and ETV5, serve as targets for those T

cells. Immune escape by Ag loss or mutation is less likely to occur if immunity

is directed against altered self-proteins that are involved in malignant

transformation. Therefore, vaccines based on modified tumor cells such as

triomas hold promise for immunotherapy of CLL and other malignancies. Polyvalent

vaccines originally designed as individualized therapeutics may be more broadly

applicable, at least in patients showing similar Ag patterns.

PMID: 18779747