Recent progress in chimeric antigen receptor-modified T-cell(CAR-T cell) technology in cancer therapy is extremely promising, especially in the treatment of patients with B-cell acute lymphoblastic leukemia. In contra...Recent progress in chimeric antigen receptor-modified T-cell(CAR-T cell) technology in cancer therapy is extremely promising, especially in the treatment of patients with B-cell acute lymphoblastic leukemia. In contrast, due to the hostile immunosuppressive microenvironment of a solid tumor, CAR T-cell accessibility and survival continue to pose a considerable challenge, which leads to their limited therapeutic efficacy. In this study, we constructed two anti-MUC1 CAR-T cell lines. One set of CAR-T cells contained SM3 single chain variable fragment(sc Fv) sequence specifically targeting the MUC1 antigen and co-expressing interleukin(IL) 12(named SM3-CAR). The other CAR-T cell line carried the SM3 sc Fv sequence modified to improve its binding to MUC1 antigen(named p SM3-CAR) but did not co-express IL-12. When those two types of CAR-T cells were injected intratumorally into two independent metastatic lesions of the same MUC1+ seminal vesicle cancer patient as part of an interventional treatment strategy, the initial results indicated no side-effects of the MUC1 targeting CAR-T cell approach, and patient serum cytokines responses were positive. Further evaluation showed that p SM3-CAR effectively caused tumor necrosis, providing new options for improved CAR-T therapy in solid tumors.展开更多
AIM： To investigate the expressions of MUC1 and MUC5AC in intrahepatic cholangiocarcinoma （ICC）. Association of expressions of mucins MUC1 and MUC5AC with clinical findings, metastasis, and survival of the liver fl...AIM： To investigate the expressions of MUC1 and MUC5AC in intrahepatic cholangiocarcinoma （ICC）. Association of expressions of mucins MUC1 and MUC5AC with clinical findings, metastasis, and survival of the liver fluke-associated ICC patients was determined. METHODS： The expressions of MUC1 and MUC5AC mucins were examined by immunohistochemical staining in 87 cases of histologically-proven ICC. The expressions of mucins in relationship between clinicopathological significance and prognosis of the patients were evaluated. RESULTS： Fifty-two patients （60%） exhibited both MUC1 and MUCSAC expressions, whereas 31% expressed either MUC1 or MUC5AC, and 9% expressed neither. High MUC1 immunoreactivity displayed a significant correlation wibh tumor progression as reflected by vascular invasion （P〈0.001）, whereas high expression of MUC5AC significantly correlated with neural invasion （P = 0.022） and advanced ICC stage （P = 0.008）. Patients with high expression of MUC1 had a significantly shorter survival （P = 0.0002）. According to multivariate analyses, MUC1 reactivity （P = 0.026）, histological grading and stage of tumor represented the least probability of survival. CONCLUSION： MUC1 is overexpressed in liver flukeassociated cholangiocarcinoma and relates to vascular invasion and poor prognosis, whereas MUC5AC mucin is neoexpressed and relates to neural invasion and advanced ICC stage. High MUC1 expression in tumor may be useful for predicting the poor outcome of ICC patients.展开更多
基金supported by the Priority Academic Program Development of Jiangsu Higher Education Institutions, the National Natural Science Foundation of China (31471283)
文摘Recent progress in chimeric antigen receptor-modified T-cell(CAR-T cell) technology in cancer therapy is extremely promising, especially in the treatment of patients with B-cell acute lymphoblastic leukemia. In contrast, due to the hostile immunosuppressive microenvironment of a solid tumor, CAR T-cell accessibility and survival continue to pose a considerable challenge, which leads to their limited therapeutic efficacy. In this study, we constructed two anti-MUC1 CAR-T cell lines. One set of CAR-T cells contained SM3 single chain variable fragment(sc Fv) sequence specifically targeting the MUC1 antigen and co-expressing interleukin(IL) 12(named SM3-CAR). The other CAR-T cell line carried the SM3 sc Fv sequence modified to improve its binding to MUC1 antigen(named p SM3-CAR) but did not co-express IL-12. When those two types of CAR-T cells were injected intratumorally into two independent metastatic lesions of the same MUC1+ seminal vesicle cancer patient as part of an interventional treatment strategy, the initial results indicated no side-effects of the MUC1 targeting CAR-T cell approach, and patient serum cytokines responses were positive. Further evaluation showed that p SM3-CAR effectively caused tumor necrosis, providing new options for improved CAR-T therapy in solid tumors.
基金Supported by the Thailand Research Fund, No. BRG/06/2544Royal Golden Jubilee PhD Program Grant, No. PHD/0045/2542 to Boonla C and Wongkham S
文摘AIM： To investigate the expressions of MUC1 and MUC5AC in intrahepatic cholangiocarcinoma （ICC）. Association of expressions of mucins MUC1 and MUC5AC with clinical findings, metastasis, and survival of the liver fluke-associated ICC patients was determined. METHODS： The expressions of MUC1 and MUC5AC mucins were examined by immunohistochemical staining in 87 cases of histologically-proven ICC. The expressions of mucins in relationship between clinicopathological significance and prognosis of the patients were evaluated. RESULTS： Fifty-two patients （60%） exhibited both MUC1 and MUCSAC expressions, whereas 31% expressed either MUC1 or MUC5AC, and 9% expressed neither. High MUC1 immunoreactivity displayed a significant correlation wibh tumor progression as reflected by vascular invasion （P〈0.001）, whereas high expression of MUC5AC significantly correlated with neural invasion （P = 0.022） and advanced ICC stage （P = 0.008）. Patients with high expression of MUC1 had a significantly shorter survival （P = 0.0002）. According to multivariate analyses, MUC1 reactivity （P = 0.026）, histological grading and stage of tumor represented the least probability of survival. CONCLUSION： MUC1 is overexpressed in liver flukeassociated cholangiocarcinoma and relates to vascular invasion and poor prognosis, whereas MUC5AC mucin is neoexpressed and relates to neural invasion and advanced ICC stage. High MUC1 expression in tumor may be useful for predicting the poor outcome of ICC patients.
