ObjectivesTo evaluate the rate of tuberculosis (TB) in biologic users for rheumatic diseases in South Africa, the effectiveness of our latent TB infection (LTBI) programme, risk factors and outcome.MethodsTB cases were collected from the South African Biologics Registry (SABIO), rheumatologists and pharmaceutical companies. Demographics, LTBI screening and treatment, biological and disease modifying antirheumatic drug (DMARD) therapies, TB diagnosis and outcomes were recorded.Results96 TB cases were collected from 1999 to June 2017: rheumatoid arthritis 55, ankylosing spondylitis 27, psoriatic arthritis 4, and juvenile inflammatory arthritis 10. The TB rate was 1240/100 000 person years for biologic users (n=96) versus the biologic naive cohort of 0/100 000 years with an incidence rate difference of 0.0124 (p<0.0001). 60/96 had pulmonary and 36/96 had extra-pulmonary TB. Reactivation TB occurred in 45/96 cases. TB occurred in all biologics licenced in South Africa, the majority in monoclonal inhibitors (1683/100 000 person years) compared with etanercept (861/100 000 person years) and non-tumour necrosis factor (TNF) inhibitors (681/100 000 person years). The incidence rate ratio for monoclonal inhibitors compared with etanercept was 1.96 (p=0.005) and 2.47 (p=0.002) compared with non-TNF inhibitors with no significant difference between non-TNF inhibitors and etanercept (p=0.336). From those (12.9%) who screened LTBI positive, 14 developed TB, while the majority (77) screened LTBI negative. Black race, male sex, younger age and residence in the Western Cape were statistical risk factors. Two drug resistant TB cases and six deaths occurred.ConclusionReactivation and new onset TB is a significant risk for all biologics users in SA. Screening for LTBI is an imperative preventative strategy.

2016-06-27·Journal of Experimental Medicine1区 · 医学

Combined IL-21–primed polyclonal CTL plus CTLA4 blockade controls refractory metastatic melanoma in a patient

1区 · 医学

Article

作者: Yee, Cassian ; Shibuya, Kendall ; Thompson, John A. ; Wagener, Felecia ; Greenberg, Philip D. ; Wolchok, Jedd D. ; Lee, Sylvia M. ; Lai, Ivy ; Roberts, Ilana M. ; Bhatia, Shailender ; Sloan, Heather L. ; Cao, Jianhong ; Margolin, Kim A. ; Chapuis, Aude G.

Adoptive transfer of peripheral blood–derived, melanoma-reactive CD8+ cytotoxic T lymphocytes (CTLs) alone is generally insufficient to eliminate bulky tumors. Similarly, monotherapy with anti-CTLA4 infrequently yields sustained remissions in patients with metastatic melanoma. We postulated that a bolus of enhanced IL-21–primed polyclonal antigen-specific CTL combined with CTLA4 blockade might boost antitumor efficacy. In this first-in-human case study, the combination successfully led to a durable complete remission (CR) in a patient whose disease was refractory to both monoclonal CTL and anti-CTLA4. Long-term persistence and sustained anti-tumor activity of transferred CTL, as well as responses to nontargeted antigens, confirmed mutually beneficial effects of the combined treatment. In this first-in-human study, Chapuis et al. demonstrate that the combination of adoptive cellular therapy with CTLA4 blockade induces long-term remission in a melanoma patient resistant to both modalities administered serially and individually.

2007-05-01·Human Gene Therapy2区 · 医学

Local and Distant Immune-Mediated Control of Colon Cancer Growth with Fusogenic Membrane Glycoproteins in Combination with Viral Oncolysis

2区 · 医学

Article

作者: Hoffmann, Dennis ; Bayer, Wibke ; Wildner, Oliver

We evaluated whether the expression of measles virus fusogenic membrane glycoproteins H and F (MV-FMG), encoded by a herpes simplex virus type 1 (HSV-1) amplicon vector, can serve with or without viral oncolysis (G47Delta) and facultative irinotecan chemotherapy, alone or in combination with the monoclonal epidermal growth factor receptor (EGFR) inhibitory antibody cetuximab, as a platform for inducing tumor-specific immune responses against colon cancer. We demonstrated in vitro that MV-FMG expression in murine cells resulted in cell-cell fusion and synergistically enhanced the cytotoxicity of irinotecan alone or in combination with cetuximab. In a bilateral syngeneic subcutaneous MC38 and Colon26 tumor model in C57BL/6 and BALB/c mice we assessed both the effect on directly vector-treated tumors and the effect on contralateral, not directly vector-treated tumors. We demonstrated that the combination of three treatment components with or without cetuximab resulted in the best volume reduction of both directly vector-treated and not directly vector-treated tumors as well as pronounced infiltration of both tumor types with natural killer cells, macrophages, and T cells. T cells of these animals exhibited strong ex vivo cytotoxic activity against the tumor cells, indicating that the antineoplastic effect on untreated tumors was mediated by an antitumor immune response. Preexisting immunity against HSV-1 or measles virus had no detrimental effect on overall treatment efficacy. Our data indicate that MV-FMG expression in combination with viral oncolysis with or without clinically relevant chemotherapy for colon cancer treatment warrants further investigation.

100 项与 CD45RB mAb 相关的药物交易

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适应症	最高研发状态	国家/地区	公司	日期
器官移植排斥	药物发现	美国	Amgen, Inc.	-
器官移植排斥	药物发现	美国	Research Corporation Technologies, Inc.	-
多发性硬化症	药物发现	美国	Amgen, Inc.	-
多发性硬化症	药物发现	美国	Research Corporation Technologies, Inc.	-