PDF(Pubmed)
Abstract：
Cancer vaccines strive to induce robust, antigen-targeted, T-cell-mediated immune responses but have struggled to produce meaningful regression in solid tumors. An autologous cell vaccine, SQZ-PBMC-HPV, was developed by SQZ Biotechnologies using microfluidic squeezing technology to load PBMCs with HPV16 E6 and E7 antigens in HLA-A*02+ patients. The SQZ-PBMC-HPV-101 Phase 1 trial (NCT04084951) enrolled patients with incurable HPV16+ cancers. Here, we present a post hoc analysis of the relationship between Posttreatment CD8+ T cell infiltration and patient outcomes. SQZ-PBMC-HPV was administered as monotherapy every 3 weeks. Tumor samples were collected pre-dose and post-dose 4 weeks after treatment start. Biomarkers including CD8, MHC-I, E6, E7, GZMB, and Ki67 were evaluated by immunohistochemistry, immunofluorescence, and RNA in situ hybridization, and were correlated with clinical response, survival, and drug product composition. Eighteen patients had paired pre- and post-dose biopsies. Six (33%) had an increase in CD8+ T cell density in tumor parenchyma between screening and C2D8. Patients with increased CD8+ T cell density had improved disease control rate (66.7% vs 16.7%) and median overall survival (606.5 days vs 170.0 days, p = 0.0078). Drug product was significantly enriched for higher T cells and lower monocytes in the increased CD8+ T cell density group. In patients with incurable HPV16+ solid tumors treated with SQZ-PBMC-HPV, an increase in CD8+ T cell density within the tumor parenchyma was associated with superior disease control rate and overall survival. The product composition for patients with increased CD8+ T cell density was enriched for T cells.
摘要：
癌症疫苗努力诱导健壮的，抗原靶向，T细胞介导的免疫反应，但一直在努力在实体瘤中产生有意义的消退。一种自体细胞疫苗,SQZ-PBMC-HPV,由SQZBiotechnologies开发，使用微流体挤压技术在HLA-A*02+患者中加载具有HPV16E6和E7抗原的PBMC。SQZ-PBMC-HPV-1011期试验（NCT04084951）纳入了无法治愈的HPV16+癌症患者。这里,我们对治疗后CD8+T细胞浸润与患者预后之间的关系进行了事后分析.SQZ-PBMC-HPV作为单一疗法每3周施用。在治疗开始后4周,在给药前和给药后收集肿瘤样品。生物标志物包括CD8、MHC-I、E6,E7,GZMB,和Ki67通过免疫组织化学进行评估，免疫荧光，和RNA原位杂交，并与临床反应相关，生存,和药物产品组成。18名患者进行了配对的给药前和给药后活检。在筛选和C2D8之间,六个(33%)在肿瘤实质中CD8+T细胞密度增加。CD8+T细胞密度增加的患者疾病控制率(66.7%vs16.7%)和中位总生存期(606.5天vs170.0天,p=0.0078）。在增加的CD8+T细胞密度组中,药物产品显著富集了较高的T细胞和较低的单核细胞。在使用SQZ-PBMC-HPV治疗的无法治愈的HPV16实体瘤患者中，肿瘤实质内CD8+T细胞密度的增加与优越的疾病控制率和总生存期相关.针对具有增加的CD8+T细胞密度的患者的产物组合物对T细胞进行富集。
