这项针对晚期、难治性、转移性乳腺癌的 I/IIa 期开放标签、单组临床试验在美国的六个医疗中心进行。我们重复接种经辐照的 SV-BR-1-GM，这是一种具有抗原呈递活性的乳腺癌细胞系，经过改造可释放粒细胞巨噬细胞集落刺激因子 (GM-CSF)，给药前给予低剂量环磷酰胺，给药后给予低剂量环磷酰胺。剂量局部干扰素α。入组了 26 名患者； 23 人（88.5%）接种了疫苗，总共接种了 79 次。注意到 6 起 4 级和 1 起 5 级不良事件（判断与 SV-BR-1-GM 无关）。 16 名可评估患者中有 8 名实现疾病控制（疾病稳定 [SD]）；图 4 显示了转移灶的客观消退，其中 1 名患者的 20 个肺部病灶中有 20 个几乎完全消退。所有回归的患者的人类白细胞抗原 (HLA) 与 SV-BR-1-GM 相匹配；无反应者在匹配和不匹配之间平均分配（p = .01，卡方），并且具有 ≥2 个 HLA 与 SV-BR-1-GM 匹配 (n = 6) 与临床获益相关。对念珠菌抗原和 SV-BR-1-GM 的迟发型超敏反应 (DTH) 测试分别在 11 名 (42.3%) 和 13 名 (50%) 患者中产生阳性反应 (≥5mm)。对外周循环肿瘤细胞 (CTC) 和癌症相关巨噬细胞样细胞 (CAML) 的定量显示，CAML 的下降与无进展生存期的改善显着相关（PFS；4.1 个月与 1.8 个月，p==.0058 ）。通过治疗，10 名患者中有 8 名显着上调 CTC/CAML 上的程序性细胞死亡配体 1 (PD-L1) (p = .0012)。这些观察结果支持 Bria-IMT 方案的安全性，证明了临床回归，暗示了 HLA 匹配的作用，并确定了监测外周血中 CAML 的可能价值。

This Phase I/IIa open-label, single-arm clinical trial addressing advanced, refractory, metastatic breast cancer was conducted at six medical centers in the United States. We repeated inoculations with irradiated SV-BR-1-GM, a breast cancer cell line with antigen-presenting activity engineered to release granulocyte-macrophage colony-stimulating factor (GM-CSF), with pre-dose low-dose cyclophosphamide and post-dose local interferon alpha. Twenty-six patients were enrolled; 23 (88.5%) were inoculated, receiving a total of 79 inoculations. There were six Grade 4 and one Grade 5 adverse events noted (judged unrelated to SV-BR-1-GM). Disease control (stable disease [SD]) occurred in 8 of 16 evaluable patients; 4 showed objective regression of metastases, including 1 patient with near-complete regressions in 20 of 20 pulmonary lesions. All patients with regressions had human leukocyte antigen (HLA) matches with SV-BR-1-GM; non-responders were equally divided between matching and nonmatching (p = .01, Chi-squared), and having ≥2 HLA matches with SV-BR-1-GM (n = 6) correlated with clinical benefit. Delayed-type hypersensitivity (DTH) testing to candida antigen and SV-BR-1-GM generated positive responses (≥5 mm) in 11 (42.3%) and 13 (50%) patients, respectively. Quantifying peripheral circulating tumor cells (CTCs) and cancer-associated macrophage-like cells (CAMLs) showed that a drop in CAMLs was significantly correlated with an improvement in progression-free survival (PFS; 4.1 months vs. 1.8 months, p = .0058). Eight of 10 patients significantly upregulated programmed cell death ligand 1 (PD-L1) on CTCs/CAMLs with treatment (p = .0012). These observations support the safety of the Bria-IMT regimen, demonstrate clinical regressions, imply a role for HLA matching, and identify a possible value for monitoring CAMLs in peripheral blood.