CSPG4-specific immunity and survival prolongation in dogs with oral malignant melanoma immunized with human CSPG4 DNA.
CSPG4-specific immunity and survival prolongation in dogs with oral malignant melanoma immunized with human CSPG4 DNA.
复制标题
DOI：
10.1158/1078-0432.ccr-13-3042
复制
发表时间：
2014-07-15
期刊：
影响因子：
--
通讯作者：
Cavallo F
中科院分区：
文献类型：
--
作者：
Riccardo F;Iussich S;Maniscalco L;Lorda Mayayo S;La Rosa G;Arigoni M;De Maria R;Gattino F;Lanzardo S;Lardone E;Martano M;Morello E;Prestigio S;Fiore A;Quaglino E;Zabarino S;Ferrone S;Buracco P;Cavallo F
由于犬(C)恶性黑色素瘤(MM)与人类有许多相似之处，因此是评估新治疗策略疗效的有价值的模型。该模型用于评价人(H)硫酸软骨素蛋白多糖-4(CSPG4)DNA疫苗的免疫原性、安全性和治疗效果。HCSPG4和cCSPG4氨基酸序列之间的同源性超过80%的事实为在CMM模型中使用hCSPG4 DNA疫苗提供了理论基础。手术切除CSPG4阳性口腔多发性骨髓瘤II-III期的狗每月接受肌肉注射，然后立即进行电穿孔(电接种)，持续至少6个月，最长20个月。对疫苗的免疫原性、安全性和治疗效果进行了评价。HCSPG4电子疫苗接种没有引起临床相关的局部或全身副作用，并导致14只接种疫苗的狗与13只未接种疫苗的狗相比，总体和无病存活时间显著延长。所有接种疫苗的狗都产生了针对hCSPG4和cCSPG4的抗体。七只接种疫苗的狗也接受了cCSPG4特异性T细胞反应的测试，只有两只狗产生了可检测到的干扰素-γ反应。针对CSPG4的异种电疫苗能够克服宿主对“自身”抗原的无反应性，并似乎在治疗CMM方面有效，为将其转化为人类临床环境奠定了基础。
Due to the many similarities with its human counterpart, canine (c) malignant melanoma (MM) is a valuable model in which to assess the efficacy of novel therapeutic strategies. The model is herein used to evaluate the immunogenicity, safety and therapeutic efficacy of a human (h) chondroitin sulfate proteoglycan-4 (CSPG4) DNA-based vaccine. The fact that homology between hCSPG4 and cCSPG4 amino-acidic sequences stands at over 80% provides the rationale for using a hCSPG4 DNA vaccine in the cMM model. Dogs with stage II-III surgically resected CSPG4-positive oral MM were subjected to monthly intramuscular plasmid administration which was followed immediately by electroporation (electrovaccination) for at least six, and up to twenty, months. The immunogenicity, safety and therapeutic efficacy of the vaccine have been evaluated. hCSPG4 electrovaccination caused no clinically relevant local or systemic side effects and resulted in significantly longer overall and disease-free survival times in 14 vaccinated dogs as compared to 13 non-vaccinated controls. All vaccinated dogs developed antibodies against both hCSPG4 and cCSPG4. Seven vaccinated dogs were also tested for a cCSPG4-specific T cell response and only two gave a detectable interferon (IFN)-γ response. Xenogeneic electrovaccination against CSPG4 is able to overcome host unresponsiveness to the “self” antigen and appears to be effective in treating cMM, laying the foundation for its translation to a human clinical setting.