An NKT mediated autologous vaccine generates CD4 T-cell-dependent potent antilymphoma immunity
An NKT mediated autologous vaccine generates CD4 T-cell-dependent potent antilymphoma immunity
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DOI：
10.1182/blood-2006-12-061309
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发表时间：
2007-09-15
期刊：
影响因子：
20.3
通讯作者：
Dong, Chen
中科院分区：
文献类型：
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作者：
Chung, Yeonseok;Qin, Hong;Dong, Chen
大多数淋巴瘤患者在抗体或化疗后复发，强调需要有效的疫苗接种方法。自体肿瘤是用于疫苗的患者特异性肿瘤抗原的理想来源；然而，它们的免疫原性差一直是实践中的主要障碍。自然杀伤T （NKT）细胞最近成为自身免疫和肿瘤免疫监视的重要调节因子。在这里，我们展示了激活NKT细胞的自体淋巴瘤疫苗在实验小鼠中产生肿瘤特异性保护性免疫。单次接种α -半乳糖神经酰胺（α GC）负载的A20淋巴瘤细胞可引起有效的抗肿瘤免疫。这种疫苗接种策略也能在a20小鼠中诱导肿瘤显著消退。重要的是，原发肿瘤接种的幸存者都对肿瘤的再攻击有抵抗力，这表明已经建立了适应性记忆免疫。耗竭和过继转移研究揭示了传统CD4(+) T细胞而非CD8(+) T细胞在介导抗肿瘤免疫中的排他性作用。此外，我们在接种疫苗的小鼠中发现了正常的造血区室。因此，NKT配体负载淋巴瘤引发持久有效的抗肿瘤免疫，可以进一步发展为针对人类淋巴瘤的患者和肿瘤特异性免疫疗法。
Relapses occurring in most patients with lymphoma after antibody or chemotherapy highlight a need for effective vaccination approaches. Autologous tumors are ideal sources of patient-specific tumor antigens for vaccines; however, their poor immunogenicity has been a major obstacle in practice. Natural killer T (NKT) cells have recently emerged as crucial regulators of autoimmunity and tumor immunosurveillance. Here, we show that an autologous lymphoma vaccine that activates NKT cells generated tumor-specific protective immunity in experimental mice. Single vaccination with alpha-galactosylceramide (alpha GC)-loaded A20 lymphoma cells elicited effective antitumor immunity against tumor challenge. This vaccination strategy also induced significant tumor regression in A20-bearing mice. Importantly, the survivors from primary tumor inoculation were all resistant to tumor rechallenge, indicative of established adaptive memory immunity. Depletion as well as adoptive transfer studies revealed an exclusive role of conventional CD4(+) but not CD8(+) T cells in mediating antitumor immunity. In addition, we found normal hematopoietic compartments in the vaccinated mice. Therefore, NKT ligand-loaded lymphoma elicits long-lasting and effective antitumor immunity, which can be further developed as patient- and tumor-specific immunotherapy against human lymphomas.