Allogeneic nonmyeloablative hematopoietic cell transplantation in metastatic colon cancer: tumor-specific T cells directed to a tumor-associated antigen are generated in vivo during GVHD
Allogeneic nonmyeloablative hematopoietic cell transplantation in metastatic colon cancer: tumor-specific T cells directed to a tumor-associated antigen are generated in vivo during GVHD
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DOI：
10.1182/blood-2005-10-3945
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发表时间：
2006-05-01
期刊：
影响因子：
20.3
通讯作者：
Aglietta, M
中科院分区：
文献类型：
--
作者：
Carnevale-Schianca, F;Cignetti, A;Aglietta, M
进行了一项初步研究，以评估非清髓性异基因造血细胞移植（HCT）在结直肠癌（CRC）中的安全性和活性，并确定是否诱导出针对肿瘤相关抗原（TAA）的T细胞反应。15名转移性结直肠癌患者在接受非清髓性预处理方案后，接受了来自人类白细胞抗原（HLA）匹配的同胞的HCT。所有患者均成功植入，在第 +56天供体T细胞嵌合率中位数为72%。8名患者发生了II至IV级急性移植物抗宿主病（GVHD）。尽管在HCT前疾病进展，但分别有1名和3名患者观察到部分缓解和疾病稳定超过90天。用癌胚抗原（CEA）特异性HLA - A*0201五聚体对6名结直肠癌患者评估了TAA特异性T细胞的诱导情况。在3名发生GVHD的患者中，有3名检测到CEA特异性CD8(+) T细胞，但在3名未发生GVHD的患者中未检测到。在9名因非结直肠癌诊断而接受移植且发生GVHD的对照患者中，也未检测到。CEA特异性T细胞的抗肿瘤活性也在体外得到验证。在一名患者中，CEA特异性T细胞的诱导与血清CEA水平降低和部分缓解相关。因此，与异基因HCT相关的移植物抗宿主反应可触发针对CEA的特异性T细胞的产生，这可能与临床反应相关。
A pilot study was conducted to evaluate safety and activity of nonmyeloablative allogeneic hematopoietic cell transplantation (HCT) in colorectal carcinoma (CRC) and to determine whether a T-cell response to a tumor-associated antigen (TAA) was induced. Fifteen patients with metastatic CRC underwent HCT from human leukocyte antigen (HLA)-matched siblings after a nonmyeloablative conditioning regimen. All patients engrafted with a median donor T-cell chimerism of 72% at day +56. Eight patients experienced grades II to IV acute graft-versus-host disease (GVHD). Despite progressive disease before HCT, partial remission and disease stabilization longer than 90 days were observed in 1 and 3 patients, respectively. Induction of TAA-specific T cells was evaluated with a carcinoembryonic antigen (CEA)-specitic HLAA*0201 pentamer in 6 patients with CRC. CEA-specific CD8(+) T cells were detected in 3 of 3 patients concomitant with GHVD onset, but not in 3 of 3 patients without GVHD. They were also not detected in 9 of 9 control patients with GVHD who received transplants for diagnoses other than CRC. Antitumor activity of CEA-specific T cells was also validated in vitro. In one patient, the induction of CEA-specific T cells was associated with a decrease of serum CEA levels and a partial response. Thus, graft-versus-host reactions associated with allogeneic HCT can trigger the generation of T cells specific for CEA, and this may be associated with a clinical response.