背景:SV-BR-1-GM,来自患有2级(中分化)乳腺癌的患者,是具有抗原呈递细胞特性的分泌GM-CSF的乳腺癌细胞系。SV-BR-1-GM和下一代版本涵盖了几项未决和授权专利。
方法:我们报告了开放标签阶段I的发现,在3例乳腺癌和1例卵巢癌受试者中使用经辐照的SV-BR-1-GM细胞进行的单臂初步研究。在接种之前,低剂量静脉内环磷酰胺,然后将干扰素-α2b注射到SVBR-1-GM接种部位。我们评估了细胞和体液免疫反应,并测量SV-BR-1-GMHLA等位基因的表达水平。
结果:治疗通常是安全且耐受性良好的。免疫反应普遍引起。4例患者中有3例的总生存期超过33个月。正如以前报道的那样,一名患者肺部转移迅速消退,乳房,和软组织。停止治疗后,病人广泛复发,包括在大脑中。再治疗后,再次看到快速的肿瘤反应,包括脑转移完全消退。与II类HLA在促进SV-BR-1-GM的作用机制中的作用一致,该患者等位基因在HLA-DRB1和HLA-DRB3基因座处匹配SV-BR-1-GM。我们正在开发下一代SV-BR-1-GM,表达患者特异性HLA。专利申请在各个司法管辖区提交。到目前为止,一个被授予,在日本。
结论:使用SV-BR-1-GM细胞的全细胞免疫治疗方案可诱导转移性乳腺癌的消退。我们基于SV-BR-1-GM的预测作用机制开发知识产权,为癌症患者开发额外的全细胞免疫疗法。
BACKGROUND: SV-BR-1-GM, derived from a patient with grade 2 (moderately differentiated) breast cancer, is a GM-CSF-secreting breast cancer cell line with properties of antigen-presenting cells. SV-BR-1-GM and next-generation versions are covered by several pending and granted patents.
METHODS: We report findings from an open-label phase I, single-arm pilot study with irradiated SV-BR-1-GM cells in 3 breast and 1 ovarian cancer subjects. Inoculations were preceded by lowdose intravenous cyclophosphamide and followed by interferon-alpha2b injections into the SVBR- 1-GM inoculation sites. We assessed both cellular and humoral immune responses, and measured expression levels of SV-BR-1-GM HLA alleles.
RESULTS: Treatment was generally safe and well tolerated. Immune responses were elicited universally. Overall survival was more than 33 months for three of the four patients. As previously reported, one patient had prompt regression of metastases in lung, breast, and soft tissue. Following cessation of treatment, the patient relapsed widely, including in the brain. Upon retreatment, rapid tumor response was again seen, including complete regression of brain metastases. Consistent with a role of Class II HLA in contributing to SV-BR-1-GM\'s mechanism of action, this patient allele-matched SV-BR-1-GM at the HLA-DRB1 and HLA-DRB3 loci. We are in the process of developing next-generation SV-BR-1-GM, expressing patient-specific HLAs. Patent applications were filed in various jurisdictions. Thus far, one is granted, in Japan.
CONCLUSIONS: A whole-cell immunotherapy regimen with SV-BR-1-GM cells induced regression of metastatic breast cancer. We develop intellectual property based on SV-BR-1-GM\'s predicted mechanism of action to develop additional whole-cell immunotherapies for cancer patients.