Neoantigen and tumor antigen-specific immunity transferred from immunized donors is detectable early after allogeneic transplantation in myeloma patients.
Neoantigen and tumor antigen-specific immunity transferred from immunized donors is detectable early after allogeneic transplantation in myeloma patients.
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在骨髓瘤患者中进行同种异体移植后，可以早期检测到从免疫供体转移的新抗原和肿瘤抗原特异性免疫力。
DOI：
10.1038/bmt.2012.132
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发表时间：
2013
影响因子：
4.8
通讯作者：
Bishop,MR
中科院分区：
文献类型：
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作者：
Foglietta,M;Neelapu,SS;Kwak,LW;Jiang,Y;Nattamai,D;Lee,S-T;Fowler,DH;Sportes,C;Gress,RE;Steinberg,SM;Vence,LM;Radvanyi,L;Dwyer,KC;Qazilbash,MH;Bryant,RNK;Bishop,MR
为了提高同种异体造血SCT （HSCT）的治疗指数，我们在干细胞采集前用受体来源的克隆骨髓瘤Ig，独特型（Id）作为肿瘤抗原，结合锁眼帽皮血青素（KLH）免疫10例hla匹配的兄弟姐妹供体。疫苗接种对捐赠者和接受者都是安全的。供体来源的klh和id特异性体液、中枢记忆和效应记忆t细胞反应在造血干细胞移植后第30天可检测到，在大多数受者中，移植后接种3个月疫苗可增强。一名患者在加强疫苗接种前死亡。具体而言，在完成治疗后，8/9的骨髓瘤患者有持续的id特异性免疫反应，5/9的疾病状态有所改善。尽管调节性T细胞在接种疫苗后增加，但它们并不影响免疫反应。在中位潜在随访期为74个月时，6例患者存活，10例患者的中位PFS为28.5个月，中位OS尚未达到。我们的研究结果提供了新抗原和肿瘤抗原特异性体液和细胞免疫可以安全地诱导造血干细胞供体并被动转移到受体的原理证明。这种一般策略可用于减少恶性肿瘤的复发和增强对同种异体造血干细胞移植后感染的保护。
To enhance the therapeutic index of allogeneic hematopoietic SCT (HSCT), we immunized 10 HLA-matched sibling donors before stem cell collection with recipient-derived clonal myeloma Ig, idiotype (Id), as a tumor antigen, conjugated with keyhole limpet hemocyanin (KLH). Vaccinations were safe in donors and recipients. Donor-derived KLH-and Id-specific humoral and central and effector memory T-cell responses were detectable by day 30 after HSCT and were boosted by post-transplant vaccinations at 3 months in most recipients. One patient died before booster vaccinations. Specifically, after completing treatment, 8/9 myeloma recipients had persistent Id-specific immune responses and 5/9 had improvement in disease status. Although regulatory T cells increased after vaccination, they did not impact immune responses. At a median potential follow-up period of 74 months, 6 patients are alive, the 10 patients have a median PFS of 28.5 months and median OS has not been reached. Our results provide proof of principle that neoantigen and tumor antigen-specific humoral and cellular immunity could be safely induced in HSCT donors and passively transferred to recipients. This general strategy may be used to reduce relapse of malignancies and augment protection against infections after allogeneic HSCT.