Conjugation of lymphoma idiotype to CD40 antibody enhances lymphoma vaccine immunogenicity and antitumor effects in mice
Conjugation of lymphoma idiotype to CD40 antibody enhances lymphoma vaccine immunogenicity and antitumor effects in mice
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DOI：
10.1182/blood-2011-05-355461
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发表时间：
2012-03-01
期刊：
影响因子：
20.3
通讯作者：
Heath, Andrew W.
中科院分区：
文献类型：
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作者：
Carlring, Jennifer;Szabo, Marika J.;Heath, Andrew W.
基于肿瘤独特型（Id）的淋巴瘤个体化免疫治疗显示，40%-50%的滤泡性淋巴瘤患者出现抗独特型体液免疫反应，50%-75%的滤泡性淋巴瘤患者出现细胞免疫反应，表明该疗法在临床上是成功的。我们开发了一种新型淋巴瘤疫苗，由与肿瘤独特型 A20 化学缀合的抗 CD40 抗体 (ADX40) 组成，并在小鼠淋巴瘤模型中进行了测试。在肿瘤攻击前，单独使用 2 剂免疫原或与其他佐剂联合免疫 BALB/c 小鼠。 ADX40-Id 疫苗接种可显着延缓肿瘤生长并降低小鼠发病率。此外，注射2次ADX40-Id与使用匙孔血蓝蛋白Id+GM-CSF标准疗法注射8次获得相似的小鼠存活率。 ADX40-Id与3-O-脱酰基-4'-单磷酰脂质A共同施用进一步显着增强了疫苗功效，从而提高了总体存活率。 ADX40-Id 免疫后检测到抗 Id 特异性抗体水平升高；然而，攻击前体内 CD4 和/或 CD8 T 细胞的耗竭表明 CD8 效应 T 细胞是肿瘤保护的主要介质。本研究的结果表明，ADX40-Id结合疫苗是作为独立疫苗或与目前获得许可的佐剂联合用于淋巴瘤免疫治疗的潜在候选者。 （血。2012；119（9）：2056-2065）
Personalized immunotherapy of lymphoma based on tumor idiotype (Id) has shown anti-idiotype humoral immune responses in 40%-50% and cellular immune responses in 50%-75% of follicular lymphoma patients, indicating that this therapy can be clinically successful. We have developed a novel vaccine against lymphoma consisting of an anti-CD40 Ab (ADX40) chemically conjugated to the tumor idiotype A20 and tested it in a murine lymphoma model. BALB/c mice were immunized with 2 doses of immunogen alone or in conjunction with additional adjuvants before tumor challenge. ADX40-Id vaccination resulted in significantly retarded tumor growth and reduced mouse morbidity. Moreover, similar mouse survival was obtained with 2 injections of ADX40-Id as with 8 injections using the standard therapy of keyhole limpet hemocyanin Id + GM-CSF. Co-administration of ADX40-Id with 3-O-deacyl-4'-monophosphoryl lipid A further significantly enhanced vaccine efficacy, resulting in an increased overall survival. Anti-Id-specific Abs were detected at elevated levels after ADX40-Id immunization; however, in vivo depletion of CD4 and/or CD8 T cells before challenge showed that CD8 effector T cells were the major mediators of tumor protection. The results of the present study show that the ADX40-Id conjugate vaccine is a potential candidate as a stand-alone vaccine or in combination with currently licensed adjuvants for lymphoma immunotherapy. (Blood. 2012; 119(9): 2056-2065)