Recently,bispecific T-cell engagers(BiTEs)and chimeric antigen receptor-modified T cells(CAR-Ts)have been shown to have high therapeutic efficacy in hematological tumors.CD87 is highly expressed in solid tumors with a...Recently,bispecific T-cell engagers(BiTEs)and chimeric antigen receptor-modified T cells(CAR-Ts)have been shown to have high therapeutic efficacy in hematological tumors.CD87 is highly expressed in solid tumors with an oncogenic function.To assess their cytotoxic effects on invasive nonfunctioning pituitary adenomas(iNFPAs),we first examined CD87 expression and its effects on the metabolism of iNFPA cells.We generated CD87-specific BiTE and CAR/IL-12 T cells,and their cytotoxic effects on iNFPAs cells and in mouse models were determined.CD87 had high expression in i NFPA tissue and cell samples but was undetected in noncancerous brain samples.CD87×CD3 BiTE and CD87 CAR/IL-12 T-cells showed antigenic specificity and exerted satisfactory cytotoxic effects,decreasing tumor cell proliferation in vitro and reducing existing tumors in experimental mice.Overall,the above findings suggest that CD87 is a promising target for the immunotherapeutic management of iNFPAs using anti-CD87 BiTE and CD87-specific CAR/IL-12 T cells.展开更多
Background: The urokinase-type plasminogen activator system which consists of a proteinase (the urokinase-type plasminogen activator, uPA), a receptor (the urokinase-type plasminogen activator receptor uPAR or CD87) a...Background: The urokinase-type plasminogen activator system which consists of a proteinase (the urokinase-type plasminogen activator, uPA), a receptor (the urokinase-type plasminogen activator receptor uPAR or CD87) and inhibitors (PAI1) is enriched in several types of tumors and involved in proteolysis, cell migration and invasion. High expression of uPA and uPAR is associated with an increased relapse rate and shorter survival in breast cancer and colorectal carcinomas. Aims: This study shed light on the expression of uPAR in adult acute myeloid leukemia (AML) and its prognostic relevance. Methods: Peripheral blood and bone marrow samples are obtained from 54 newly diagnosed AML adult patients, 20 healthy controls stained with anti CD87 and estimated on flow cytometry. Results: CD87 expression was heterogeneous in different FAB subtypes of AML with high expression in monocytic leukemia (M4/M5) (P value 0.001). High expression of CD87 was associated with shorter survival and poor response to therapy (P = 0.028, 0.002 respectively). The most discriminating cut off value of CD87 expression was 20%, patients with less than 20% expression had 4.6 times better treatment outcome than those with more than or equal to 20%. On the multivariate analysis, CD87 was the most significant single variable that affect treatment outcome compared to total leucocytic count, hemoglobin level, platelets count, cytogenetic and FLT expression. Summary/Conclusion: High CD87 expression is an independent prognostic parameter associated with poor response and shorter overall survival in adult AML patients.展开更多
基金supported by the National Key Research and Development Program of China(2021YFE0114300)the National Key Basic Research Program of China(973 Program)(2014CB541603)+1 种基金the National High Technology Research and Development Program of China(863 Program)(2013AA020106)the National Natural Science Foundation of China(82171475,82170799)。
文摘Recently,bispecific T-cell engagers(BiTEs)and chimeric antigen receptor-modified T cells(CAR-Ts)have been shown to have high therapeutic efficacy in hematological tumors.CD87 is highly expressed in solid tumors with an oncogenic function.To assess their cytotoxic effects on invasive nonfunctioning pituitary adenomas(iNFPAs),we first examined CD87 expression and its effects on the metabolism of iNFPA cells.We generated CD87-specific BiTE and CAR/IL-12 T cells,and their cytotoxic effects on iNFPAs cells and in mouse models were determined.CD87 had high expression in i NFPA tissue and cell samples but was undetected in noncancerous brain samples.CD87×CD3 BiTE and CD87 CAR/IL-12 T-cells showed antigenic specificity and exerted satisfactory cytotoxic effects,decreasing tumor cell proliferation in vitro and reducing existing tumors in experimental mice.Overall,the above findings suggest that CD87 is a promising target for the immunotherapeutic management of iNFPAs using anti-CD87 BiTE and CD87-specific CAR/IL-12 T cells.
文摘Background: The urokinase-type plasminogen activator system which consists of a proteinase (the urokinase-type plasminogen activator, uPA), a receptor (the urokinase-type plasminogen activator receptor uPAR or CD87) and inhibitors (PAI1) is enriched in several types of tumors and involved in proteolysis, cell migration and invasion. High expression of uPA and uPAR is associated with an increased relapse rate and shorter survival in breast cancer and colorectal carcinomas. Aims: This study shed light on the expression of uPAR in adult acute myeloid leukemia (AML) and its prognostic relevance. Methods: Peripheral blood and bone marrow samples are obtained from 54 newly diagnosed AML adult patients, 20 healthy controls stained with anti CD87 and estimated on flow cytometry. Results: CD87 expression was heterogeneous in different FAB subtypes of AML with high expression in monocytic leukemia (M4/M5) (P value 0.001). High expression of CD87 was associated with shorter survival and poor response to therapy (P = 0.028, 0.002 respectively). The most discriminating cut off value of CD87 expression was 20%, patients with less than 20% expression had 4.6 times better treatment outcome than those with more than or equal to 20%. On the multivariate analysis, CD87 was the most significant single variable that affect treatment outcome compared to total leucocytic count, hemoglobin level, platelets count, cytogenetic and FLT expression. Summary/Conclusion: High CD87 expression is an independent prognostic parameter associated with poor response and shorter overall survival in adult AML patients.
