Purpose: Cancer/testis antigens have emerged as attractive targets for cancer immunotherapy. Clinical studies have targeted MAGE-A3, a prototype antigen that is a member of the MAGE-A family of antigens, in melanoma and lung carcinoma. However, these studies have not yet had a significant impact due to poor CD8+ T cell immunogenicity, platform toxicity, or perhaps limited target antigen availability. In this study we develop an improved MAGE-A immunogen with cross-reactivity to multiple family members. Experimental Design: In this study we analyzed MAGE-A expression in The Cancer Genome Atlas and observed that many patients express multiple MAGE-A isoforms, not limited to MAGE-A3, simultaneously in diverse tumors. Based on this, we designed an optimized consensus MAGE-A DNA vaccine capable of cross-reacting with many MAGE-A isoforms, and tested immunogenicity and anti-tumor activity of this vaccine in a relevant autochthonous melanoma model. Results: Immunization of this MAGE-A vaccine by electroporation in C57Bl/6 mice generated robust IFN-γ and TNF-α CD8+ T cell responses as well as cytotoxic CD107a/IFN-γ/T-bet triple-positive responses against multiple isoforms. Furthermore, this MAGE-A DNA immunogen generated a cross-reactive immune response in 14 out of 15 genetically diverse, outbred mice. We tested the anti-tumor activity of this MAGE-A DNA vaccine in Tyr::CreER;BRAFCa/+;Ptenlox/lox transgenic mice that develop melanoma upon tamoxifen induction. The MAGE-A DNA therapeutic vaccine significantly slowed tumor growth and doubled median mouse survival. Conclusions: These results support the clinical use of consensus MAGE-A immunogens with the capacity to target multiple MAGE-A family members to prevent tumor immune escape.

Objective. Gouty arthritis (GA) is a noninfectious inflammatory disease characterized by self-limited and severe pain. Huzhang Tongfeng granule is one of the most effective traditional Chinese medicines in the treatment of acute GA. However, its effects on the inflammatory factors in the process of acute gout inflammation remain unknown. In the present study, we aimed to evaluate the effect of Huzhang Tongfeng granule on the expressions of Cyr61 and related inflammatory factors in both experimental gout models in vivo and in vitro. Methods. Huzhang Tongfeng granule was provided by the pharmaceutical preparation room of Yueyang Hospital of Integrated Traditional Chinese and Western Medicine. The expressions of Cyr61, IL-1β, TNF-α, and IL-6 in monosodium urate- (MSU-) induced rat models and fibroblast-like synoviocytes (FLSs) were determined by RT-PCR, Western blotting analysis, ELISA, immunohistochemistry, and hematoxylin and eosin staining. Results. Huzhang Tongfeng granule could downregulate the expressions of IL-1β, TNF-α, and IL-6 to some extent by inhibiting the expression of Cyr61. Conclusions. Collectively, our findings indicated that Cyr61 was highly expressed in rat models of gout. By inhibiting the expression of Cyr61, Huzhang Tongfeng granule could partially attenuate the inflammation induced by MSU crystal.

Cytokines in serum and signal transducers in the psoriatic lesions alter with various CM syndromes of psoriasis. The results provide scientific basis for the treatment based on syndrome differentiation of CM in treating psoriasis vulgaris.