ALLOGENEIC LEUKOCYTE INFUSIONS FOR BREAST CANCER

同种异体白细胞输注治疗乳腺癌

• 批准号: 2885536
• 负责人: SCOTT I BEARMAN
• 金额: $ 15.1万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-07-07 至 2001-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2885536
• 关键词: autologous transplantation; bone marrow; breast neoplasms; cell transplantation; clinical research; clinical trial phase I; female; flow cytometry; fluorescent in situ hybridization; histocompatibility; homologous transplantation; human subject; human therapy evaluation; injection /infusion; leukocytes; neoplasm /cancer immunotherapy; neoplasm /cancer relapse /recurrence; phenotype

DESCRIPTION: (Applicant's Abstract) In this project, the applicant will study the feasibility of administering allogeneic leukocytes to breast cancer patients who have relapsed after autologous transplantation. There are considerable data supporting a graft-versus-tumor effect in selected hematologic malignancies (CML, AML, multiple myeloma). However, definitive evidence of such an effect in breast cancer has not been demonstrated. A number of institutions are studying allogeneic stem cell transplantation for metastatic breast cancer to determine whether such an effect exists and whether it can be exploited. He is studying whether allogeneic peripheral blood leukocytes obtained from HLA-identical or 1-antigen mismatched siblings can engraft without preparative therapy in patients with breast cancer who have relapsed after autologous transplantation (Protocol 97-017). UPN 677 was a 62-year-old female with metastatic breast cancer who underwent autologous stem cell transplantation in April 1997 after high-dose chemotherapy using paclitaxel, cyclophosphamide, cisplatin and BCNU. In February 1998 she progressed in bone and one month later developed hepatic metastases. On June 5, 1998 she received an infusion of G-CSF-mobilized peripheral blood, documented by fluorescence in-situ hybridization (FISH), was 1-2% for the first 2 weeks after infusion and then began to rise, reaching 51% on August 13. She died on August 20, 1998 without evidence for an antitumor effect. However, multilineage engraftment was documented by identification of granulocytes, monocytes and lymphocytes of donor origin. In addition, myeloid (CFU-GM) and erythroid (BFU-E) progenitors were grown in methylcellulose and all colonies evaluated were of donor origin by FISH. Tumor obtained from the liver post-mortem was found to contain 4% donor cells by FISH. These cells have been identified as CD3+, CD19-. The applicant proposes to further evaluate this therapeutic modality in additional relapsed breast cancer patients. The following correlative studies are proposed: (1) evaluation of donor chimerism by FISH or short tandem repeat assays in circulating leukocytes, marrow and progenitor cells, (2) evaluation of immunocompetence pre- and post-infusion by both immunophenotyping peripheral blood leukocytes and by specific immune function studies, (3) evaluation of graft-versus-tumor activity by examination for infiltrating donor cells.

描述：（申请人的摘要）在这个项目中，申请人将学习 给乳腺癌施用同种异白细胞的可行性 自体移植后复发的患者。有 大量数据支持选定的移植物肿瘤效应 血液学恶性肿瘤（CML，AML，多发性骨髓瘤）。但是，确定性 尚未证明这种在乳腺癌中产生这种影响的证据。一个数字 机构正在研究同种异体干细胞移植 转移性乳腺癌以确定是否存在这种影响以及是否存在 它可以被利用。他正在研究同种异体外周血是否 从HLA-ISSIDATIC或1抗原不匹配的兄弟姐妹获得的白细胞可以 在没有制备治疗的乳腺癌患者中植入 自体移植后复发（协议97-017）。 UPN 677是一个 62岁的女性患有自体茎的转移性乳腺癌 高剂量化疗后，细胞移植于1997年4月 紫杉醇，环磷酰胺，顺铂和BCNU。 1998年2月她 在骨骼中进展，一个月后发展出肝转移。 6月5日， 1998年，她收到了记录的G-CSF动物外围血液的注入 通过荧光原位杂交（FISH），最初2周为1-2％ 输液后，然后开始上升，8月13日达到51％。她死于 1998年8月20日，没有抗肿瘤作用的证据。但是，多琳 通过鉴定粒细胞，单核细胞和 供体起源的淋巴细胞。另外，髓样（CFU-GM）和红细胞 （BFU-E）祖细胞在甲基纤维素中生长，并评估所有菌落 是鱼的起源。从肝后获得的肿瘤为 发现通过鱼包含4％的供体细胞。这些细胞已被确定为 CD3+，CD19-。申请人建议进一步评估这种治疗方法 其他复发性乳腺癌患者的方式。下列 提出了相关研究：（1）通过鱼或鱼类对供体嵌合的评估或 短串联重复测定在循环白细胞，骨髓和祖细胞中 细胞，（2）评估两者的免疫电位前后免疫电位 免疫表型外周血白细胞和特定免疫功能 研究，（3）通过考察评估移植物与肿瘤活性的评估 浸润供体细胞。