Antigen mimicry as an effective strategy to induce CSPG4-targeted immunity in dogs with oral melanoma: a veterinary trial.
Antigen mimicry as an effective strategy to induce CSPG4-targeted immunity in dogs with oral melanoma: a veterinary trial.
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DOI：
10.1136/jitc-2021-004007
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发表时间：
2022-05
影响因子：
10.9
通讯作者：
中科院分区：
文献类型：
--
作者：
黑色素瘤是人类最致命的皮肤癌。常规疗法的疗效有限，考虑到免疫检查点抑制剂仅在低百分比的患者中诱导持久的临床应答，总体应答仍然不令人满意。这促使我们开发一种采用肿瘤抗原硫酸软骨素蛋白聚糖（CSPG）4作为靶点的疫苗接种策略。为了克服宿主对自身抗原CSPG 4的无反应性，我们已经利用了通过系统进化的CSPG 4序列的保守性，因此我们使用了基于包含CSPG 4的人（Hu）和狗（Do）部分的嵌合DNA分子的疫苗（HuDo-CSPG 4）。我们在一项前瞻性、非随机、兽医临床试验中检测了其安全性和免疫原性（主要目的），沿着其治疗有效性（次要结局），该试验招募了80只手术切除的CSPG 4阳性II-IV期口腔黑色素瘤患者。接种疫苗的狗产生抗Do-CSPG 4和Hu-CSPG 4免疫应答。有趣的是，免疫犬的抗体滴度与总体存活率显著相关。我们的数据表明，与仅用常规疗法治疗的对照相比，HuDo-CSPG 4疫苗接种可能有助于提高接种疫苗的狗的存活率。HuDo-CSPG 4佐剂疫苗接种在患有口腔黑色素瘤的狗中是安全的和免疫原性的，对疾病进程具有潜在的有益作用。由于天然存在的犬肿瘤作为癌症免疫治疗反应的预测模型的能力，这些数据可能代表了将这种方法转化为治疗CSPG 4阳性黑色素瘤亚型的人类患者的基础。
Melanoma is the most lethal form of skin cancer in humans. Conventional therapies have limited efficacy, and overall response is still unsatisfactory considering that immune checkpoint inhibitors induce lasting clinical responses only in a low percentage of patients. This has prompted us to develop a vaccination strategy employing the tumor antigen chondroitin sulfate proteoglycan (CSPG)4 as a target. To overcome the host’s unresponsiveness to the self-antigen CSPG4, we have taken advantage of the conservation of CSPG4 sequence through phylogenetic evolution, so we have used a vaccine, based on a chimeric DNA molecule encompassing both human (Hu) and dog (Do) portions of CSPG4 (HuDo-CSPG4). We have tested its safety and immunogenicity (primary objectives), along with its therapeutic efficacy (secondary outcome), in a prospective, non-randomized, veterinary clinical trial enrolling 80 client-owned dogs with surgically resected, CSPG4-positive, stage II–IV oral melanoma. Vaccinated dogs developed anti-Do-CSPG4 and Hu-CSPG4 immune response. Interestingly, the antibody titer in vaccinated dogs was significantly associated with the overall survival. Our data suggest that there may be a contribution of the HuDo-CSPG4 vaccination to the improvement of survival of vaccinated dogs as compared with controls treated with conventional therapies alone. HuDo-CSPG4 adjuvant vaccination was safe and immunogenic in dogs with oral melanoma, with potential beneficial effects on the course of the disease. Thanks to the power of naturally occurring canine tumors as predictive models for cancer immunotherapy response, these data may represent a basis for the translation of this approach to the treatment of human patients with CSPG4-positive melanoma subtypes.
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影响因子：
2.6
作者：
Cheema, P. K.;Burkes, R. L.
通讯作者：
Burkes, R. L.
影响因子：
2.1
作者：
Coy, J.;Caldwell, A.;Dow, S.
通讯作者：
Dow, S.
DOI：
10.1016/j.tvjl.2011.02.020
发表时间：
2011-11-01
期刊：
Veterinary journal (London, England : 1997)
影响因子：
--
作者：
Mayayo, Saray Lorda;Prestigio, Simone;Iussich, Selina
通讯作者：
Iussich, Selina
影响因子：
2.1
作者：
LeBlanc AK;Atherton M;Bentley RT;Boudreau CE;Burton JH;Curran KM;Dow S;Giuffrida MA;Kellihan HB;Mason NJ;Oblak M;Selmic LE;Selting KA;Singh A;Tjostheim S;Vail DM;Weishaar KM;Berger EP;Rossmeisl JH;Mazcko C
通讯作者：
Mazcko C
影响因子：
10.1
作者：
Conti, Laura;Bolli, Elisabetta;Cavallo, Federica
通讯作者：
Cavallo, Federica