Immunotherapy of hematological malignancies or solid tumors by administration of
monoclonal antibodies or T-cells engineered to express chimeric antigen receptors or T-cell
receptors (TCRs) has demonstrated clinical efficacy. However, antigen-loss tumor escape
variants and the absence of currently targeted antigens on several malignancies hampers
the widespread application of immunotherapy. We have isolated a TCR targeting a peptide
of the intracellular B-cell specific transcription factor BOB1 presented in the context of HLA
B*07:02. TCR gene transfer installed BOB1-specificity and reactivity onto recipient T-cells.
TCR-transduced T-cells efficiently lysed primary B-cell leukemia, mantel cell lymphoma an... More
Immunotherapy of hematological malignancies or solid tumors by administration of
monoclonal antibodies or T-cells engineered to express chimeric antigen receptors or T-cell
receptors (TCRs) has demonstrated clinical efficacy. However, antigen-loss tumor escape
variants and the absence of currently targeted antigens on several malignancies hampers
the widespread application of immunotherapy. We have isolated a TCR targeting a peptide
of the intracellular B-cell specific transcription factor BOB1 presented in the context of HLA
B*07:02. TCR gene transfer installed BOB1-specificity and reactivity onto recipient T-cells.
TCR-transduced T-cells efficiently lysed primary B-cell leukemia, mantel cell lymphoma and
multiple myeloma in vitro. We also observed recognition and lysis of healthy BOB1
expressing B-cells. In addition, strong BOB1-specific proliferation could be demonstrated for
TCR-modified T-cells upon antigen encounter. Furthermore, clear in vivo antitumor reactivity
was observed of BOB1-specific TCR-engineered T-cells in a xenograft mouse model of
established multiple myeloma. Absence of reactivity towards a broad panel of BOB1
negative but HLA-B*07:02pos nonhematopoietic and hematopoietic cells indicated no off
target toxicity. Therefore, administration of BOB1-specific TCR-engineered T-cells may
provide novel cellular treatment options to patients suffering from B-cell malignancies
including multiple myeloma.
