LBPO.CL04 · 临床研究 · Late-Breaking

在接受现成型癌症"暗物质"疫苗DPV-001联合抗PD-1±抗GITR治疗的头颈鳞状细胞癌（HNSCC）患者中寻找抗癌免疫的靶点

Search for targets of anti-cancer immunity in patients receiving an off-the-shelf cancer's dark matter vaccine, DPV-001, combined with anti-PD-1 +/- anti-GITR in head and neck squamous cell cancer (HNSCC)

编号 LB425 展板 15 时间 4/22 09:00–12:00 区域 Section 51 主讲 Guo Hui Gan

分会场 Late-Breaking Research: Clinical Research 4

该海报暂无可下载的资料 AACR 官方页面

作者与单位 Authors & Affiliations

Traci Hilton¹, Ryan Meng², Guo Hui Gan², Tarsem Moudgil², Christopher Paustian², Noah Simons², Venkatesh Rajamanickam², Shawn M. Jensen², Elie Adwani², Sierra J. Smith², Matthew H. Taylor², Olivier Fesneau², Thomas M. Duhen², Irene Shih², Myungkyu Jang², Annie Long², Abigail Staeck², Tijana Jovanovic², Brady Bernard², Christie Tanisha², Noriko Iwamoto³, Yuriko Minegishi⁴, Koji Ueda⁴, William L. Redmod², Lessli M. Rushforth², Takashi Shimada³, Patrick Rethwisch², Carlo B. Bifulco², Hong-ming Hu¹, Walter J. Urba², Yoshinobu Koguchi⁵, Marcus A. Couey⁶, Richard B. Bell², Jianguo Huang², Eric Tran², Brian Piening², Rom Leidner², Bernard A. Fox²

¹UbiVac, Portland, OR,²Earle A. Chiles Research Institute, Portland, OR,³Shimadzu Corporation, Kyoto, Japan,⁴Japanese Foundation for Cancer Research, Tokyo, Japan,⁵Ohio State University, Portland, OR,⁶Boston University, Boston, MA

摘要 Abstract

中文摘要

背景：尽管癌症基因组学和免疫治疗取得进展，大多数癌症疫苗策略仅靶向有限的一组经典或突变癌抗原，仅捕获了肿瘤抗原性的一小部分。恶性细胞产生大量、在很大程度上尚未被探索的非经典"暗物质"抗原，这些抗原源自暗基因组。许多此类抗原常缺失于正常组织，并因致癌失调而富集，甚至可能是致癌失调的原因。我们已开发出一种疫苗策略DPV-001，其中包含经典抗原和400余种暗物质癌抗原，并在一项针对HNSCC患者的联合免疫治疗试验中评估了DPV-001。这项1b期试验使应答率较抗PD-1的历史经验提高了两倍，并促使人们鉴定治疗性抗癌免疫反应所靶向的抗原。在此，我们报告所采用的策略以及从该试验患者中鉴定所靶向癌抗原的初步结果。方法：符合条件的患者按1:1随机分组，接受DPV-001联合或不联合GITR激动剂抗体（INCAGN-1876），所有患者自第15天起接受序贯的PD-1阻断（retifanlimab）。采用HuScan™噬菌体展示免疫沉淀（PhIP）分析患者血清，覆盖29,371种人类蛋白质和剪接异构体。以抗体产生作为抗原特异性T细胞反应的替代指标。DPV-001中的经典和暗物质癌抗原以及一个HNSCC HLA肽组数据库正被用于聚焦研究接受DPV-001患者所识别的靶点。结果：在11例患者中评估了PhIP检测到的抗体，其中包括第2臂（接受GITR）的7例患者。输注后一周的GITR血清水平在3例患者中被表征为低（平均163 reads/million），在4例患者中为高（平均585 reads/million）（p < 0.002）。GITR低与GITR高组在比较吸烟史、CPS评分或体重时无显著差异。在基线时，GITR低组针对NCBI 35.1蛋白质组靶点的强抗体信号（>10倍单纯磁珠最大信号）显著少于（平均148）GITR高组（平均596，p=0.002）或第1臂（无GITR，平均406，p=0.042）。针对HNSCC抗原的B细胞和T细胞反应的表征仍在进行中。结论：这项纳入18例患者、评估DPV-001联合序贯PD-1±GITR的试验显示出有前景的应答率。鉴定在获得客观临床应答的患者中所靶向的抗原，可能有助于开发新一代癌症疫苗。

查看英文原文 English abstract

Background: Despite advances in cancer genomics and immunotherapy, most cancer vaccine strategies target a limited set of canonical or mutated cancer antigens, capturing only a fraction of tumor antigenicity. Malignant cells generate a vast, largely unexplored repertoire of non-canonical “dark matter” antigens arising from the dark genome. Many of these antigens are frequently absent from normal tissues and enriched by and possibly responsible for oncogenic dysregulation. We have developed a vaccine strategy, DPV-001, that includes canonical and more than 400 dark matter cancer antigens and have evaluated DPV-001 in a combination immunotherapy trial for patients with HNSCC. This phase 1b trial tripled response rates over historical experience with anti-PD-1 and encouraged identification of the antigens targeted by the therapeutic anti-cancer immune response. Here we report the strategy we are employing and preliminary results on identifying targeted cancer antigens from patients on this trial. Methods: Eligible patients were randomized 1:1 to receive DPV-001 with or without a GITR agonist antibody (INCAGN-1876), with all patients receiving sequential PD-1 blockade (retifanlimab) starting day 15. Patient sera were analyzed by HuScan™ phage display immunoprecipitation (PhIP), covering 29,371 human proteins and splice isoforms. Antibody development was used as a surrogate for antigen-specific T cell responses. The canonical and dark matter cancer antigens in DPV-001, and an HNSCC HLA peptidome database, are being used to focus investigations of targets recognized by patients that received DPV-001. Results: PhIP detected Ab was assessed in 11 patients, including 7 patients from Arm 2 (received GITR). One-week post-infusion GITR serum levels were characterized as low (Avg 163 reads/million) in 3 patients and high (avg 585 reads/million) in 4 patients (p < 0.002). There were no significant differences between GITR Low and GITR High groups when comparing their smoking history, CPS score, or body weight. At baseline, patients in the GITR Low group had significantly fewer strong Ab signals (Avg 148) to the NCBI 35.1 proteome targets (>10x beads only maximum signal) compared to the GITR High group (avg 596, p=0.002) or Arm 1 (No-GITR, Avg 406, p=0.042). Characterization of B and T cell responses to HNSCC antigens is ongoing. Conclusions: This 18 pt trial of DPV-001 and sequenced PD-1 +/- GITR shows a promising RR. Identification of the antigens targeted in patients with objective clinical responses may enable development of a new generation of cancer vaccines.

利益披露 Disclosure

T. Hilton, UbiVac Employment. R. Meng, None.. G. Gan, None.. T. Moudgil, None.. C. Paustian, None.. N. Simons, None.. V. Rajamanickam, None.. S. M. Jensen, None.. E. Adwani, None.. S. J. Smith, None. M. H. Taylor, Immatics ). Exelixis Other, Consulting (honoraria). Providence Portland Medical Center Patent. Pfizer ). BMS ). Merck ). Moderna ). O. Fesneau, None.. T. M. Duhen, None.. I. Shih, None.. M. Jang, None.. A. Long, None.. A. Staeck, None.. T. Jovanovic, None.. B. Bernard, None.. C. Tanisha, None. N. Iwamoto, Shimadzu Corporation ). Y. Minegishi, None. K. Ueda, Shimadzu Corporation ). W. L. Redmod, Inhibrx ). Bristol-Myers Squibb ). Shimadzu Corporation ). Galecto Therapeutics ), Patent. Vesselon Other, Advisory board. Medicenna Other, Medicenna. L. M. Rushforth, None.. T. Shimada, None.. P. Rethwisch, None. C. B. Bifulco, PrimeVax Stock, Other, Scientific Advisor. BioAI Stock, Scientific Advisor. Pictor Labs Stock, Scientific Advisor. SironaDx Stock, Scientific Advisor. Sanofi; Agilent; Roche; Incendia; Bristol-Myers Squibb; Merck Other, Consultant/advisor. Hamamatsu ), Travel. Illumina ). H. Hu, ImmuXell Employment, g., Board of Directors, non-salaried role). W. J. Urba, None.. Y. Koguchi, None.. M. A. Couey, None. R. B. Bell, Incyte ). Merck, Regeneron; Bristol-Myers Squibb; AstraZeneca; Bright Peak therapeutics; AdelaBio ). J. Huang, None. E. Tran, Pathfinder Oncology Other, Consultant. AstraZeneca Other, Consultant (past, term ended December 2025). B. Piening, None. R. Leidner, Bristol-Myers Squibb; AstraZeneca; Incyte ). Vir; RAPT; CDR-Life Other, Advisory boards. Lucid Diagnostics Patent. B. A. Fox, Akoya ). Bristol-Myers Squibb ), Other, Scientific advisory board. Hamamatsu ). Incyte ), Other, Scientific advisory board. Lunaphore ). Merck ), Other, Scientific advisory board. Navinci ). Shimadzu Corporation ). UbiVac Employment, g., Board of Directors, non-salaried role), Stock, ). Abalytics Stock Option, Other, Scientific advisory board. PrimeVax Stock Option, Other, Scientific advisory board.

← 返回 AACR 2026 检索