Backgrounds: Multiple myeloma (MM) is a hematooncologic disease caused by malignant transformation of Blymphocytes, their clonal proliferation and accumulation of terminal stages plasmocytes (myeloma cells). Recently, high-dose chemotherapy with autologous hematopoietic transplantation has been considered standard treatment for patients with advanced stages of multiple myeloma. Such treatment delays relapse but it is not curative and almost all patients ultimately develop recurrent disease.
Design and Subjects: Based on preclinical and clinical it is evident that myeloma-reactive T lymphocytes play an important role in extending time of remission after autologous transplantation. Myeloma-reactive T lymphocytes have been shown to be a promising approach in adoptive cellular immunotherapy aside autologous transplantation of bone marrow graft. Analysis of their TCR repertoire gives information on the spectrum of recognized antigens.
Methods and Results: Dendritic cells loaded with apoptotic bodies from myeloma cells have been used to stimulate autologous T lymphocytes. Activated myeloma-specific T cells were identified and expanded. After mRNA isolation the anchored reverse transcription using a modified version of the SMART method was done. PCR product was cloned into plasmid vector, transformed in bacterial cells and individual clonotypes were sequenced. Oligoclonality of the TCR receptor was demonstrated in myeloma specific in vitro expanded T lymphocytes, in one case a monoclonal population of tumor specific T cells was found. These findings support the of myeloma specific antigens stimulating only certain autologous T lymphocytes.
Conclusions: Structural characterization of the TCR receptor of myeloma specific clones represents a promising method for immunologic monitoring of cancer treatment.