Cancer-testis antigen SLLP1 represents a promising target for the immunotherapy of multiple myeloma
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Cancer-testis antigen SLLP1 represents a promising target for the immunotherapy of multiple myeloma. / Yousef, Sara; Heise, Johanna; Lajmi, Nesrine; Bartels, Katrin; Kröger, Nicolaus; Luetkens, Tim; Atanackovic, Djordje.
In: J TRANSL MED, Vol. 13, 20.07.2015, p. 197.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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T1 - Cancer-testis antigen SLLP1 represents a promising target for the immunotherapy of multiple myeloma
AU - Yousef, Sara
AU - Heise, Johanna
AU - Lajmi, Nesrine
AU - Bartels, Katrin
AU - Kröger, Nicolaus
AU - Luetkens, Tim
AU - Atanackovic, Djordje
PY - 2015/7/20
Y1 - 2015/7/20
N2 - BACKGROUND: Most patients with multiple myeloma (MM) will relapse after an initial response and eventually succumb to their disease. This is due to the persistence of chemotherapy-resistant tumor cells in the patients' bone marrow (BM) and immunotherapeutic approaches could contribute to eradicating these remaining cells. We evaluated SLLP1 as a potential immunotherapeutic target for MM.METHODS: We determined SLLP1 expression in myeloma cell lines and 394 BM samples from myeloma patients (n = 177) and BM samples from healthy donors (n = 11). 896 blood samples and 64 BM samples from myeloma patients (n = 263) and blood from healthy donors (n = 112) were analyzed for anti-SLLP1 antibodies. Seropositive patients were evaluated regarding SLLP1-specific T cells.RESULTS: Most cell lines showed SLLP1 RNA and protein expression while it was absent from normal BM. Of 177 patients 41% evidenced SLLP1 expression at least once during the course of their disease and 44% of newly diagnosed patients were SLLP1-positive. Expression of SLLP1 was associated with adverse cytogenetics and with negative prognostic factors including the patient's age, number of BM-infiltrating plasma cells, serum albumin, β2-microglobulin, creatinine, and hemoglobin. Among patients treated with allogeneic stem cell transplantation those with SLLP1 expression showed a trend towards a reduced overall survival. Spontaneous anti-SLLP humoral immunity was detectable in 9.5% of patients but none of the seropositive patients evidenced SLLP1-specific T cells. However, antigen-specific T cells could readily be induced in vitro after stimulation with SLLP1.CONCLUSIONS: SLLP1 represents a promising target for the immunotherapy of MM, in particular for the adoptive transfer of T cell receptor-transduced T cells.
AB - BACKGROUND: Most patients with multiple myeloma (MM) will relapse after an initial response and eventually succumb to their disease. This is due to the persistence of chemotherapy-resistant tumor cells in the patients' bone marrow (BM) and immunotherapeutic approaches could contribute to eradicating these remaining cells. We evaluated SLLP1 as a potential immunotherapeutic target for MM.METHODS: We determined SLLP1 expression in myeloma cell lines and 394 BM samples from myeloma patients (n = 177) and BM samples from healthy donors (n = 11). 896 blood samples and 64 BM samples from myeloma patients (n = 263) and blood from healthy donors (n = 112) were analyzed for anti-SLLP1 antibodies. Seropositive patients were evaluated regarding SLLP1-specific T cells.RESULTS: Most cell lines showed SLLP1 RNA and protein expression while it was absent from normal BM. Of 177 patients 41% evidenced SLLP1 expression at least once during the course of their disease and 44% of newly diagnosed patients were SLLP1-positive. Expression of SLLP1 was associated with adverse cytogenetics and with negative prognostic factors including the patient's age, number of BM-infiltrating plasma cells, serum albumin, β2-microglobulin, creatinine, and hemoglobin. Among patients treated with allogeneic stem cell transplantation those with SLLP1 expression showed a trend towards a reduced overall survival. Spontaneous anti-SLLP humoral immunity was detectable in 9.5% of patients but none of the seropositive patients evidenced SLLP1-specific T cells. However, antigen-specific T cells could readily be induced in vitro after stimulation with SLLP1.CONCLUSIONS: SLLP1 represents a promising target for the immunotherapy of MM, in particular for the adoptive transfer of T cell receptor-transduced T cells.
U2 - 10.1186/s12967-015-0562-5
DO - 10.1186/s12967-015-0562-5
M3 - SCORING: Journal article
C2 - 26088750
VL - 13
SP - 197
JO - J TRANSL MED
JF - J TRANSL MED
SN - 1479-5876
ER -