Dinutuximab

γδ T 细胞是先天性与适应性免疫的“桥梁”细胞，具有 MHC非依赖性识别肿瘤的能力；   它们能直接杀伤肿瘤细胞，并分泌 IFN-γ、TNF-α 等细胞因子，重塑肿瘤微环境。 part 1 γδ T 细胞的基本特征 1 分类与组织分布 γδ T 细胞根据 TCR δ 链 分为：Vδ1、Vδ2、Vδ3 及少量 Vδ5；Vγ9Vδ2 T 细胞是外周血中最主要的亚群；Vδ1 和 Vδ3 T 细胞在外周血中较少，但在组织（黏膜、皮肤、肠道等）中富集。 2 单细胞转录组学揭示的异质性 Vδ2 T 细胞：存在三个胸腺发育阶段（早期 → 效应 → 细胞毒性），功能编程主要发生在出生后胸腺，外周扩增有限。   Vδ1 T 细胞：在胎儿和婴儿期占主导，克隆多样性极高；成人后受 CMV 等感染驱动，向寡克隆/私有种型转化，呈现适应性记忆特征。   组织特异性：乳腺、肺、肝脏中的 Vδ1 细胞呈现组织驻留记忆表型（CD69⁺ CD103⁺），不依赖 TCR 即可快速响应细胞因子（IL-12、IL-18）。 3 γδ T 细胞的关键抗肿瘤特性 part 2 γδ T 细胞 如何识别肿瘤？ 01   Vγ9Vδ2 T 细胞的        识别机制 识别磷抗原（如 IPP），通过 BTN3A1 和 BTN2A1 家族分子介导； 磷抗原结合 BTN3A1 的 B30.2 结构域，诱导构象变化，促使 BTN2A1 与 Vγ9 TCR 链结合； AMPK 激动剂可上调 BTN2A1/BTN3A1，增强肿瘤杀伤； Vγ9Vδ2 T 细胞高表达 CD16，可介导 ADCC。 02   Vδ1⁻ T 细胞（Vδ1、Vδ3、Vδ5）的识别机制 Vδ1 TCR 多样性高，呈现适应性免疫特征； 识别 MICA、CD1家族、MR1 等 MHC 样分子； 识别 EphA2、annexin A2、EPCR 等肿瘤相关分子； 依赖 NK 受体（如 NKG2D、DNAM-1、NKp30）识别应激配体。 03  NK 受体的作用 NKG2D 识别 MICA/B、ULBP，直接激活 γδ T 细胞； DNAM-1 识别 PVR/CD155、nectin-2/CD112，对 AML 和 CRC 靶向至关重要； NKp30/44/46 在特定刺激下诱导表达，增强肿瘤识别。 part 3 γδ T 细胞在癌症中 的功能角色 1 抗肿瘤作用（多数研究） 小鼠模型：γδ T 细胞缺失增加化学诱导肿瘤发生率； 人类肿瘤中高丰度 γδ T 细胞（尤其是 Vδ1）与良好预后相关： 三阴性乳腺癌、非小细胞肺癌、肝细胞癌、卵巢癌、胃癌、头颈癌、膀胱癌、结直肠癌等； 机制：分泌 IFN-γ、TNF-α、穿孔素、颗粒酶 B、TRAIL。 2 促肿瘤作用的罕见情况 IL-17⁺ γδ T 细胞在部分模型中促进肿瘤进展； 在 CRC 中，早期以 IFN-γ⁺ 为主（抗肿瘤），晚期向 IL-17⁺ 转化（促肿瘤）； 人 γδ T 细胞以 IFN-γ⁺ 细胞毒性表型为主，与小鼠差异显著； CRC 微环境中 γδ T 细胞可被重编程为 AREG⁺ 伤口愈合表型，促进肿瘤进展。 part 4 γδ T 细胞疗法 01 关键发现 肿瘤浸润 γδ T 细胞（尤其是 Vδ1）高表达 PD-1、TIGIT、TIM-3，但仍保留效应功能； 这些细胞不呈现典型耗竭特征，与 CD8⁺ T 细胞不同； 在肾癌、黑色素瘤、CRC 中，PD-1⁺ γδ T 细胞仍具增殖和杀伤能力。 02 ICB 对 γδ T 细胞的        增强作用 PD-L1/PD-1 或 TIGIT 阻断可增强 γδ T 细胞杀伤功能； 在卵巢癌、黑色素瘤、Merkel 细胞癌中，PD-1⁺ γδ T 细胞与ICB 治疗响应正相关； 正在进行的临床试验：NCT06212388、NCT06364800、NCT06404281。 03  生物制剂靶向    γδ T 细胞 抗 BTN3A 单抗 ICT01 可激活 Vγ9Vδ2 T 细胞，联合阿扎胞苷/维奈克拉在 AML 中显示良好耐受性与高缓解率（EVICTION 试验）。双特异性 T 细胞衔接分子（如 LAVA-1207 靶向 Vδ2×PSMA）已在转移性前列腺癌进入 I/II 期试验；Vδ1×EGFR 双特异性分子处于临床前阶段。此外，利用 γδ T 细胞高表达 CD16 的特性，可联合抗 GD2 抗体（dinutuximab）诱导 ADCC 治疗神经母细胞瘤。 04  过继 γδ T 细胞治疗 早期使用氨磷酸盐联合 IL-2 扩增 Vδ2 T 细胞的策略因扩增效率低和细胞耗竭而临床反应有限。异体 γδ T 细胞可避免 GVHD 实现“现货型”治疗，其中化疗耐药的 INB-100 在移植后患者中达 100% 一年无复发生存。课题组开发的 Vδ1 富集 DOT 细胞扩增超 1000 倍，依赖 DNAM-1/PVR 识别 AML，已进入 I/II 期试验；在结直肠癌模型中联合丁酸盐或抗 PD-1/抗 TIGIT 可进一步增强疗效。 05  CAR-γδ T 细胞与其他工程化策略 CAR-γδ T 细胞兼具 TCR 和 NK 受体的广谱识别能力，可减少免疫逃逸并实现异体现货化治疗。代表性产品包括靶向 CD20 的 ADI-001（I 期，7/9 完全缓解）、靶向 CD70 的 ADI-270（I/II 期肾癌）等。新型工程化策略包括 AbTCR（降低 CRS 风险）、TEG 细胞（将 γδ TCR 转入 αβ T 细胞）以及 CAR 与 BiTE 或 IL-15 联合的双靶向武装。 part 5 γδ T流式 1 human 外周血 2 mouse 外周淋巴结 vs 2耳皮肤 part 6 结论与展望 1 优势总结 MHC 非限制性，适用于 HLA 缺陷肿瘤； 组织归巢能力强，适合上皮来源肿瘤； 快速、广谱、多功能的免疫响应； 异体可用，便于规模化生产。 2 挑战与未来方向 实体瘤中 TME 免疫抑制（如 PGE2、IDO、galectin）需联合靶向； 需优化 CAR 信号模块以更好适配 γδ T 细胞生物学； 需开发 Vδ1 特异性衔接分子； 需更多临床数据验证持久性、安全性、抗肿瘤活性。 参考文献 https://doi.org/10.1146/annurev-immunol-083024-024653 DOI: 10.1002/eji.202170126 联系我们 7*24 h快速响应+专业技术解答，双重保障让您无后顾之忧！欢迎有实验服务/产品需求的老师随时联系（4008-526413） END 加入社群 关于福麦斯

75% 2.5-year overall survival for OST-HER2 vs. 47% pooled historical control (p = 0.003), with no new patient deaths reported since the 2-year overall survival data (75% vs. 60%, p = 0.034) Updated clinical efficacy data being added to regulatory dossiers as Company seeks early market authorizations in U.S., U.K., Europe and Australia in 2 nd half of 2026 EMA and Australia TGA (TGA) alignment achieved on early Q4-2026 3-year overall survival data, supported by biomarker data, as key approvable clinical efficacy endpoint Upcoming U.S. FDA and U.K. MHRA meetings seek alignment with EMA and TGA on Phase 2b 3-year overall survival and biomarker data to support early market access Confirmatory Phase 3 study, required to have commenced prior to grant of early market access in U.S., U.K., Europe or Australia, expected to initiate in late Q3-2026 in Australia New York and Rockville, Maryland--(News - June 2, 2026) - OS Therapies, Inc. (NYSE American: OSTX) ("OS Therapies" or "the Company") , the world leader in gene-edited, Listeria-based cancer immunotherapies, today announced that its Phase 2b trial of OST-HER2 in the prevention or delay of recurrence in fully resected, pulmonary metastatic osteosarcoma (the "Metastatic Osteosarcoma") achieved statistically significant benefit for OST-HER2 treated patients in overall survival at the 2.5-year timepoint (75% vs. 47%, p = 0.003, Figure 1 OST-HER2 vs. pooled historical control). The topline data shows improving OST-HER2 survival benefit when compared with the 2-year data ( 2-year overall survival was 75% vs. 60%, p = 0.034 ). No new patient deaths were reported between the 2 and 2.5-year timepoints in the OST-HER2 treated group. OST-HER2 data is supported by a unique, patent pending pharmacodynamic immune response biomarker signature (Antigen Presentation, NK Cell Activation, T Cell Activation, etc.) that was developed as a surrogate clinical efficacy endpoint. The Company intends to present detailed data results during the MIB Agents Factor 2026 Osteosarcoma Conference being held June 25-27, 2026 in Columbus, OH. "The osteosarcoma community is eagerly awaiting its first approved immunotherapy that has a strong safety pro activates the immune system to surveil against pulmonary recurrence," said Dr. Peter Anderson, pediatric oncologist at Cleveland Clinic Children's and member of the scientific advisory board for OS Therapies. "New treatments are needed for metastatic osteosarcoma, so I am hopeful OST-HER2 could become an option in the near future." Figure 1 - Overall Survival Kaplan-Meier Curve To view an enhanced version of this graphic, please visit: OS Therapies is now updating its ongoing U.S. and international regulatory market authorization submissions for OST-HER2 in Metastatic Osteosarcoma with this new clinical efficacy data. The European Medicines Agency (EMA) and the Australian Therapeutic Goods Administration (TGA) have already aligned on the use of 3-year overall survival data that will be available in early Q4-2026 as the key clinical efficacy data to support the Company's conditional Marketing Authorisation Applications (cMAAs), with rolling review already underway in Europe. The Company has an upcoming Type B Pre-BLA Meeting with the U.S. Food & Drug Administration (FDA) to gain alignment on use of the forthcoming 3-year overall survival to support a Biologics Licensing Application (BLA) under the Accelerated Approval Program. "The sustained survival benefit for patients treated with our immunotherapy, with no new deaths reported between the 2-year and 2.5-year timepoints, demonstrates potential durability of OST-HER2's clinical benefit for metastatic osteosarcoma patients," said Dr. Craig Eagle, Chief Medical Advisor of OS Therapies. "As we engage further with regulators on the risk-benefit of OST-HER2 treatment for patients likely to experience metastatic osteosarcoma recurrence, we believe that sustained overall survival benefit, when coupled with the biomarker data, will support early market access authorizations in late 2026. With 3-year survival data on the horizon in early Q4-2026 to support our FDA, EMA, MHRA and TGA filings for early market access, we anticipate receiving authorizations in late Q4-2026." OS Therapies also has an upcoming Type C Meeting with FDA, and a separate Scientific Advice Meeting (SAM) with the U.K.'s Medicines and Healthcare products Regulatory Agency (MHRA), both being held in early June 2026, to confirm each agency's alignment with the key design parameters already agreed upon with EMA and TGA for the confirmatory Phase 3 protocol. OST-HER2 has received Orphan Drug Designation (ODD), Fast Track Designation (FTD) and Rare Pediatric Disease Designation (RPDD) from the FDA, and ODD, FTD and ATMP from the EMA. Under the RPDD program, if the Company is granted a BLA in the United States, it will become eligible to receive a Priority Review Voucher (PRV) which it intends to sell. The Company has begun filing a BLA for OST-HER2 in pulmonary metastatic osteosarcoma with FDA under the Accelerated Approval Program for OST-HER2 and has received rolling review from the EMA. The Company also anticipates CMA decisions in Europe, the U.K. and Australia in late 2026. About OS Therapies OS Therapies is a clinical stage oncology company focused on the identification, development, and commercialization of treatments for Osteosarcoma (OS) and other solid tumors. The Company is the world leader in gene-edited, Listeria-based cancer immunotherapies. OST-HER2, the Company's lead asset, is an immunotherapy leveraging the immune-stimulatory effects of Listeria bacteria to initiate a strong immune response targeting the HER2 protein. OST-HER2 is designed to target two mutated extracellular epitopes and one mutated intracellular epitope of the HER2 oncogene, requiring only one of these three epitopes to be present in a tumor (or micro-metastasis) to trigger the desired immune response. OST-HER2 has received Orphan Drug Designation (ODD), Fast Track Designation (FTD) and Rare Pediatric Disease Designation (RPDD) from the U.S. Food & Drug Administration and has received ODD, FTD and ATMP from the European Medicines Agency. The Company reported positive data in its Phase 2b clinical trial of OST-HER2 in recurrent, fully resected, lung metastatic osteosarcoma, demonstrating clinically significant benefit in the 12-month event free survival (EFS) primary endpoint of the study and the overall survival (OS) secondary endpoint. The Company is seeking a Biologics License Application (BLA) from the U.S. FDA for OST-HER2 in osteosarcoma in 2026 and, if approved, would become eligible to receive a Priority Review Voucher that it could then sell. The Company also anticipates receiving Conditional Marketing Authorisations from the U.K.'s Medicines and Healthcare products Regulatory Agency and the EMA for OST-HER2 in 2026. OST-HER2 has completed a Phase 1 clinical study primarily in breast cancer patients, in addition to showing preclinical efficacy data in various models of breast cancer. OST-HER2 has been conditionally approved by the U.S. Department of Agriculture for the treatment of canines with osteosarcoma. The Company also anticipates reading out data from a Phase 1b study of OST-504 in castration resistant prostate cancer in the first half of 2026. In addition, OS Therapies is advancing its next-generation Antibody Drug Conjugate (ADC) and Drug Conjugates (DC), known as tunable ADC (tADC), which features tunable, tailored antibody-linker-payload candidates. This platform leverages the Company's proprietary silicone Si-Linker and Conditionally Active Payload (CAP) technology, enabling the delivery of multiple payloads per linker. For more information, please visit . Forward-Looking Statements Statements in this press release about future expectations, plans and prospects, as well as any other statements regarding matters that are not historical facts, may constitute forward-looking statements within the meaning of the federal securities laws. These forward-looking statements and terms such as "anticipate," "expect," "intend," "may," "will," "should" or other comparable terms involve risks and uncertainties because they relate to events and depend on circumstances that will occur in the future. Those statements include statements regarding the intent, belief or current expectations of OS Therapies and members of its management, as well as the assumptions on which such statements are based. OS Therapies cautions readers that forward-looking statements are based on management's expectations and assumptions as of the date of this press release and are subject to certain risks and uncertainties that could cause actual results to differ materially, including, but not limited to our expectations regarding cash runway into 2027, the potential approval of OST-HER2 by the U.S. FDA and other risks and uncertainties described in "Risk Factors" in the Company's most recent Annual Report on Form 10-K and other subsequent documents the Company files with the Securities and Exchange Commission. Any forward-looking statements contained in this press release speak only as of the date hereof, and, except as required by the federal securities laws, OS Therapies specifically disclaims any obligation to update any forward-looking statement, whether because of new information, future events or otherwise. OS Therapies Contact Information: Investor Relations Harrison Seidner, PhD WaterSeid Partners OSTX@waterseid.com Public Relations Stephanie Chen Elev8 New Media media@ostherapies.com 1 Chen F, et al. Repeat resection of pulmonary metastasis is beneficial for patients with osteosarcoma of the extremities. Interact Cardiovasc Thorac Surg. 2009 Oct;9(4):649-53. 2 Carola A.S. Arndt, et al; Inhaled Granulocyte-Macrophage Colony Stimulating Factor for First Pulmonary Recurrence of Osteosarcoma: Effects on Disease-Free Survival and Immunomodulation. A Report From the Children's Oncology Group. Clin Cancer Res 1 August 2010; 16 (15): 4024-4030. 3 Hingorani P, et al. Phase 2 study of anti-disialoganglioside antibody, dinutuximab, in combination with GM-CSF in patients with recurrent osteosarcoma: A report from the Children's Oncology Group. Eur J Cancer. 2022;172:264-275. 4 Kempf-Bielack B, et al. Osteosarcoma relapse after combined modality therapy: an analysis of unselected patients in the Cooperative Osteosarcoma Study Group (COSS). J Clin Oncol. 2005;23(3):559-568. 5 Janeway KA, et al. A Phase 2 Trial of RANKL Antibody, Denosumab, in Two Cohorts of Patients with Recurrent/Refractory Osteosarcoma, a Report from the Children's Oncology Group. Clin Cancer Res. 2026;32(1):36-44. 6 Leary SE, et al. Survival of pediatric patients after relapsed osteosarcoma: the St. Jude Children's Research Hospital experience. Cancer. 2013;119(14):2645-2653. 7 Chou AJ, et al. Treatment of osteosarcoma at first recurrence after contemporary therapy: the Memorial Sloan-Kettering Cancer Center experience. Cancer. 2005;104(10):2214-2221 . 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