Laminin Receptor Might be Vaccine Target in Early CLL

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J Immunol. 2006 Jun 1;176(11):6935-6944.

Identification of HLA-A*0201-Presented T Cell Epitopes Derived from

the Oncofetal Antigen-Immature Laminin Receptor Protein in Patients

with Hematological Malignancies.

Siegel S, Wagner A, Friedrichs B, Wendeler A, Wendel L, Kabelitz D,

Steinmann J, Barsoum A, Coggin J, Rohrer J, Dreger P, Schmitz N, Zeis

M.

General Hospital St. Georg, Department of Hematology, Hamburg,

Germany;

The oncofetal Ag immature laminin receptor (OFA-iLR) is a potential

target molecule for immunotherapeutic studies in several tumor

entities, including hematological malignancies.

In the present study, we characterize two HLA-A*0201-presented

epitopes eliciting strong OFA-iLR peptide-specific human cytotoxic T

cell (CTLs) responses in vitro. Both allogeneic HLA-A*0201-matched

and autologous CTLs recognized and killed endogenously OFA-iLR-

expressing tumor cell lines and primary malignant cells from patients

with hemopoietic malignancies in an MHC-restricted fashion but spared

nonmalignant hemopoietic cells. Spontaneous OFA-iLR peptide-specific

T cell reactivity was detectable in a significant proportion of

leukemia patients.

Interestingly, in patients with chronic lymphocytic leukemia and

multiple myeloma but not in those with acute myeloid leukemia,

significant frequencies of OFA peptide-specific CTLs could be

detected in an early stage of disease but disappeared in patients

with progressive disease.

The identification of OFA-iLR-derived peptide epitopes provides a

basis for tumor immunological studies and therapeutic vaccination

strategies in patients with OFA-iLR-expressing malignancies.

PMID: 16709854 [PubMed - as supplied by publisher]