更新于：2024-11-01

CD28

更新于：2024-11-01

基本信息

别名

CD28抗原、CD28、CD28 antigen (Tp44)

+ [4]

简介

Involved in T-cell activation, the induction of cell proliferation and cytokine production and promotion of T-cell survival. Enhances the production of IL4 and IL10 in T-cells in conjunction with TCR/CD3 ligation and CD40L costimulation (PubMed:8617933). Isoform 3 enhances CD40L-mediated activation of NF-kappa-B and kinases MAPK8 and PAK2 in T-cells (PubMed:15067037).

关联

项与 CD28 相关的药物

FR-104

靶点

CD28

作用机制

CD28抑制剂 [+1]

在研机构

Veloxis Pharmaceuticals A/S [+3]

原研机构

Effimune SA

在研适应症

器官移植排斥 [+1]

非在研适应症

脑脊髓炎 [+5]

最高研发阶段临床2期

首次获批国家/地区-

首次获批日期1800-01-20

Acazicolcept

靶点

CD28 x ICOS

作用机制

CD28抑制剂 [+1]

在研机构

Alpine Immune Sciences, Inc.

原研机构

Alpine Immune Sciences, Inc.

在研适应症

系统性红斑狼疮

非在研适应症

1型糖尿病 [+1]

最高研发阶段临床2期

首次获批国家/地区-

首次获批日期1800-01-20

REGN-5668

靶点

CD28 x MUC16

作用机制

CD28激动剂 [+1]

在研机构

Regeneron Pharmaceuticals, Inc.

原研机构

Regeneron Pharmaceuticals, Inc.

在研适应症

子宫内膜癌 [+3]

非在研适应症-

最高研发阶段临床1/2期

首次获批国家/地区-

首次获批日期1800-01-20

项与 CD28 相关的临床试验

NCT06465329 / Recruiting临床2期

A Randomized Phase 2 Platform Study to Evaluate Cemiplimab Plus Chemotherapy Versus Cemiplimab Plus Chemotherapy Plus Other Cancer Treatments for the Perioperative Treatment of Patients With Resectable Non-Small Cell Lung Cancer

This study will enroll adult participants with early-stage (stage II-IIIB) non-small cell lung cancer for whom surgery is planned.
The aim is to find out whether an investigational treatment (consisting of the immunotherapy drug cemiplimab plus chemotherapy plus a third drug) works better than cemiplimab plus chemotherapy without the additional drug.
The study is also looking at several other research questions, including:
* What are the side effects associated with the investigational treatments in comparison to the control treatment?
* Do the investigational treatments or the control treatment have an effect on the type of surgery that is performed?
* How much of the study drug(s) are in the blood at a given time?
* Does the body make antibodies against the study drugs (which could make the drugs less effective or could lead to side effects)?

开始日期2024-10-15

申办/合作机构

Regeneron Pharmaceuticals, Inc.

KCT0009580 / Not yet recruiting临床2期IIT

Phase 2a, open-label, multi-center study of GI-101A or GI-102 (CD80-IgG4 FC-IL2v) in patients with relapsed/refractory diffuse large B-cell lymphoma following anti-CD19 chimeric antigen receptor T-cell therapy (CARNATION)

开始日期2024-07-31

申办/合作机构

Asan Medical Center

NCT06139406 / Recruiting临床1期

A Phase 1, First-in-human Study of JNJ-87801493 in Combination With CD3 T-Cell Engagers in Participants With Relapsed/Refractory B-cell Non-Hodgkin Lymphoid Malignancies (NHLs)

The purpose of this study is to characterize safety and to determine the recommended phase 2 regimen (RP2R) for JNJ-87801493 in combination with T-cell engagers (TCEs) [Part A: Dose Escalation] and to further assess the safety of JNJ-87801493 at the RP2R in combination with TCEs [Part B: Dose Expansion].

开始日期2023-12-06

申办/合作机构

Janssen Research & Development LLC

100 项与 CD28 相关的临床结果

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100 项与 CD28 相关的转化医学

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0 项与 CD28 相关的专利（医药）

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12,480

项与 CD28 相关的文献（医药）

2025-01-01·Methods in Molecular Biology

Transcription Factor Analysis to Investigate Immunosenescence in Rheumatoid Arthritis Patients

Article

作者: Dada, Rima ; Kumar, Sanjeev ; Gautam, Surabhi

Rheumatoid arthritis (RA) is linked to various signs of advanced aging, such as premature immunosenescence which occurs due to decline in regenerative ability of T cells. RA T cells develop a unique aggressive inflammatory senescent phenotype with an imbalance of Th17/T regulatory (Treg) cell homeostasis and presence of CD28^- T cells. The phenotypic analysis and characterization of T cell subsets become necessary to ascertain if any functional deficiencies exist within with the help of transcription factor (TF) analysis. These subset-specific TFs dictate the functional characteristics of T-cell populations, leading to the production of distinct effector cytokines and functions. Examining the expression, activity, regulation, and genetic sequence of TFs not only aids researchers in determining their importance in disease processes but also aids in immunological monitoring of patients enrolled in clinical trials, particularly in evaluating various T-cell subsets [Th17 (CD3⁺CD4⁺IL17⁺RORγt⁺) cells and T regulatory (Treg) (CD3⁺CD4⁺CD25⁺CD127^-FOXP3⁺) cells], markers of T-cell aging [aged Th17 cells (CD3⁺CD4⁺IL17⁺RORγt⁺CD28^-), and aged Treg cells (CD3⁺CD4⁺CD25⁺CD127^-FOXP3⁺CD28^-)]. In this context, we propose and outline the protocols for assessing the expression of TFs in aged Th17 and Treg cells, highlighting the crucial aspects of this cytometric approach.

2025-01-01·Journal of Affective Disorders

Causal effects of gut microbiota, metabolites, immune cells, liposomes, and inflammatory proteins on anorexia nervosa: A mediation joint multi-omics Mendelian randomization analysis

Article

作者: Bi, Tianyu ; Li, Zeyang

BACKGROUNDAnorexia nervosa (AN) is a significant psychological disorder influenced by environmental and genetic elements. Emerging research highlights the pivotal role of the gut microbiome in the development of diverse mental health conditions. This study aims to explore the causal effects and interactions of the gut microbiome, metabolites, immune cells, lipids, and inflammatory proteins on the risk of anorexia nervosa through mediation and multi-omics Mendelian Randomization (MR) analysis.METHODSThis study used data from the FinnGen genome-wide association study (GWAS) of AN (N = 402,625), integrated with GWAS data on 473 of gut microbiota (N = 5959), 233 metabolites (N = 136,016), 731 immune cells (N = 3757), 179 lipids (N = 7174), and 91 inflammatory proteins (N = 14,824). This study used the univariate MR (UVMR), mediation MR analysis, and sensitivity analysis to assess the potential causal associations between these biomarkers and AN.RESULTSThe inverse variance weighted (IVW) results suggest that 25 gut microbiota have causal effects on AN. Firmicutes E (OR: 0.294, 95 % CI: 0.107-0.806, P = 0.017), RUG147 (OR: 0.386, 95 % CI: 0.151-0.990, P = 0.048), CAG-977 (OR: 0.562, 95 % CI: 0.378-0.837, P = 0.005), Desulfobacterota A (OR: 0.651, 95 % CI: 0.466-0.909, P = 0.012), CAG-269 sp002372935 (OR: 0.673, 95 % CI: 0.483-0.937, P = 0.019), Klebsiella (OR: 0.684, 95 % CI: 0.566-0.827, P = 0.00009), Desulfovibrionia (OR: 0.706, 95 % CI: 0.538-0.926, P = 0.012), Klebsiella pneumoniae (OR: 0.737, 95 % CI: 0.600-0.906, P = 0.004), Desulfovibrionales (OR: 0.786, 95 % CI: 0.631-0.979, P = 0.031), CAG-776 (OR: 0.787, 95 % CI: 0.632-0.980, P = 0.032), Desulfovibrionaceae (OR: 0.788, 95 % CI: 0.635-0.978, P = 0.030). 13 gut microbiota were risk factors for AN, including Parachlamydiales (OR: 3.134，95%CI: 1.185-8.287, P = 0.021), Paenibacillus J (OR: 2.366，95%CI: 1.305-4.29, P = 0.005), Gillisia (OR: 1.947，95%CI: 1.135-3.339, P = 0.016), UBA1191 (OR: 1.856，95%CI: 1.221-2.822, P = 0.004), UBA7703 (OR: 1.843，95%CI: 1.032-3.289, P = 0.039), Faecalicatena sp002161355 (OR: 1.788，95%CI: 1.114-2.870, P = 0.016), Johnsonella ignava (OR: 1.742，95%CI: 1.031-2.944, P = 0.038), Staphylococcus aureus (OR: 1.614, 95%CI: 1.007-2.588, P = 0.047), Comamonas (OR: 1.522，95%CI: 1.004-2.307, P = 0.048), Ruminococcus D (OR: 1.24，95%CI: 1.050-1.464, P = 0.011), CAG-349 (OR: 1.198，95%CI: 1.048-1.370, P = 0.008), Ruminococcus D bicirculans (OR: 1.175，95%CI: 1.001-1.379, P = 0.048), CAG-177 (OR: 1.272，95%CI: 1.077-1.503, P = 0.005). Reverse MR analysis showed that causal effect of AN on 18 gut microbiota, but to a lesser extent. 12 metabolites have causal effects on AN. There are 7 protective factors, including glucose levels (OR: 0.700, 95%CI: 0.550-0.893, P = 0.004), isoleucine levels (OR: 0.769, 95%CI: 0.602-0.983, P = 0.036), phospholipids in large VLDL (OR: 0.856, 95%CI: 0.736-0.996, P = 0.044), total lipids in large VLDL (OR: 0.860, 95%CI: 0.740-0.999, P = 0.049), total lipids in small VLDL (OR: 0.863, 95%CI: 0.751-0.992, P = 0.038), free cholesterol in small VLDL (OR: 0.86, 95%CI: 0.752-0.996, P = 0.044), and free cholesterol in medium VLDL (OR: 0.866, 95%CI: 0.752-0.998, P = 0.047). There are 5 risk factors, including estimated degree of unsaturation (OR: 1.174, 95%CI: 1.009-1.367, P = 0.039), free cholesterol to total lipids ratio in small VLDL (OR: 1.199, 95%CI: 1.017-1.414, P = 0.031), phospholipids to total lipids ratio in small VLDL (OR: 1.216, 95%CI: 1.008-1.467, P = 0.041), total cholesterol levels in small HDL (OR: 1.241, 95%CI: 1.008-1.530, P = 0.042), and phospholipids to total lipids ratio in medium VLDL (OR: 1.280, 95%CI: 1.055-1.553, P = 0.012). Reverse MR analysis showed that AN had a causal effect on 15 metabolites. Mediation analysis reveals that the estimated degree of unsaturation mediates 0.69 % of the effect of Klebsiella pneumoniae on AN. Total lipids in small VLDL mediate 0.358 % of the effect of CAG-177 on AN, with a mediated proportion of 1.490 %. The mediation proportions for Estimated degree of unsaturation and Total lipids in small VLDL are relatively small. 36 immune cells have causal effects on AN. There are 7 protective factors, including Switched memory B cells %B cell (OR: 0.892，95%CI: 0.801-0.994, P = 0.038), CD127-CD8+ T cell absolute count (OR: 0.888，95%CI: 0.789-1.000, P = 0.049), IgD + CD24- B cell (OR: 0.917，95%CI: 0.862-0.975, P = 0.006), HVEM+ T cell (OR: 0.945，95%CI: 0.894-0.999, P = 0.045), CD40 + CD14 + CD16- monocyte (OR: 0.937，95%CI: 0.882-0.996, P = 0.038), CD64 + CD14 + CD16- monocyte (OR: 0.966，95%CI: 0.939-0.993, P = 0.016), CD8+ natural killer T cells (OR: 0.911，95%CI: 0.836-0.992, P = 0.032), HLA-DR+ T cells (OR: 0.921，95%CI: 0.866-0.980, P = 0.010), CD28-CD8+ T cells (OR: 0.886，95%CI: 0.792-0.991, P = 0.034). There are 26 risk factors. Reverse MR analysis showed that AN had a causal effect on 31 immune cells. AN increases the expression levels of five types of immune cells, including CD40 + CD14-CD16+ monocytes (OR: 1.087，95%CI: 1.004-1.177, P = 0.041), PDL-1+ CD14-CD16+ monocytes (OR: 1.082，95%CI: 1.002-1.168, P = 0.046), CD45+ CD33dim HLA-DR+ cells (OR: 1.145，95%CI: 1.019-1.287, P = 0.023), CD45+ basophils (OR: 1.164，95%CI: 1.036-1.307, P = 0.011), CD8+ natural killer T cells (OR: 1.102, 95%CI: 1.015-1.196, P = 0.020), and also decreases the expression levels of 26 immune cells. 6 liposomes showed exhibit protective effects against AN, including phosphatidylcholine (18:0_20:3) levels (OR: 0.852, 95%CI: 0.740-0.981, P = 0.026), phosphatidylcholine (O-18:2_18:1) levels (OR: 0.800, 95%CI: 0.672-0.952, P = 0.012), phosphatidylinositol (18:0_18:1) levels (OR: 0.873, 95%CI: 0.773-0.986, P = 0.029), phosphatidylinositol (18:1_18:2) levels (OR: 0.844, 95%CI: 0.734-0.971, P = 0.018), sphingomyelin (d38:1) levels (OR: 0.903，95%CI: 0.820-0.995, P = 0.039), and triacylglycerol (56:4) levels (OR: 0.786, 95%CI: 0.660-0.936, P = 0.007). There are 3 risk factors, including diacylglycerol (16:1_18:1) levels (OR: 1.208, 95%CI: 1.040-1.404, P = 0.014), phosphatidylcholine (18:1_18:3) levels (OR: 1.237, 95%CI: 1.003-1.526, P = 0.047), and phosphatidylinositol (16:0_20:4) levels (OR: 1.148, 95%CI: 1.003-1.314, P = 0.045). Reverse MR analysis showed that AN had a causal effect on 3 phosphatidylcholine (15:0_18:2) levels (OR: 1.075, 95%CI: 1.001-1.154, P = 0.048), phosphatidylcholine (O-16:2_18:0) levels (OR: 1.078, 95%CI: 1.002-1.159, P = 0.043), and triacylglycerol (51:1) levels (OR: 0.919, 95%CI: 0.850-0.994, P = 0.035). 6 inflammatory proteins have causal effects on AN, with protective factors including Glial cell line-derived neurotrophic factor levels (OR: 0.822，95%CI: 0.692-0.978, P = 0.027) and Interleukin-15 receptor subunit alpha levels (OR: 0.886, 95%CI: 0.789-0.995, P = 0.041) and risk factors including CC motif chemokine 4 levels (OR: 1.126, 95%CI: 1.011-1.254, P = 0.031), Interleukin-12 subunit beta levels (OR: 1.135, 95%CI: 1.033-1.248, P = 0.008), Monocyte chemoattractant protein-1 levels (OR: 1.152, 95%CI: 1.010-1.314, P = 0.035), and Sulfotransferase 1A1 levels (OR: 1.166, 95%CI: 1.006-1.351, P = 0.042). Reverse MR analysis showed that AN had a causal effect on Transforming growth factor-alpha (OR: 1.054，95%CI: 1.010-1.101, P = 0.016).CONCLUSIONSThis study used large-scale and novel GWAS data, for the first time reveals through mediation analysis and multi-omics MR analysis the roles of gut microbiota, metabolites, immune cells, lipids, and inflammatory proteins in the pathogenesis of AN. These findings provide new biomarkers and targets for further prevention and treatment strategies.

2024-12-31·OncoImmunology

Expression of CD39 is associated with T cell exhaustion in ovarian cancer and its blockade reverts T cell dysfunction

Article

作者: Seubert, Elisa ; Koch-Nolte, Friedrich ; Qi, Minyue ; Wellbrock, Jasmin ; Witt, Marius ; Schmalfeldt, Barbara ; Menzel, Stephan ; Sturmheit, Tabea ; Brauneck, Franziska ; Weimer, Pauline ; Bokemeyer, Carsten ; Ding, Yi ; Fiedler, Walter ; Hell, Louisa ; Oliveira-Ferrer, Leticia

Immune exhaustion is a hallmark of ovarian cancer. Using multiparametric flow cytometry, the study aimed to analyze protein expression of novel immunological targets on CD3⁺ T cells isolated from the peripheral blood (n = 20), malignant ascites (n = 16), and tumor tissue (n = 6) of patients with ovarian cancer (OVCA). The study revealed an increased proportion of effector memory CD8⁺ T cells in OVCA tissue and malignant ascites. An OVCA-characteristic PD-1^high CD8⁺ T cell population was detected, which differed from PD-1^lowCD8⁺ T cells by increased co-expression of TIGIT, CD39, and HLA-DR. In addition, these OVCA-characteristic CD8⁺ T cells showed reduced expression of the transcription factor TCF-1, which may also indicate reduced effector function and memory formation. On the contrary, the transcription factor TOX, which significantly regulates terminal T cell-exhaustion, was found more frequently in these cells. Further protein and gene analysis showed that CD39 and CD73 were also expressed on OVCA tumor cells isolated from solid tumors (n = 14) and malignant ascites (n = 9). In the latter compartment, CD39 and CD73 were also associated with the expression of the "don't eat me" molecule CD24 on tumor cells. Additionally, ascites-derived CD24⁺EpCAM⁺ tumor cells showed a higher frequency of CD39⁺ or CD73⁺ cells. Furthermore, CD39 expression was associated with unfavorable clinical parameters. Expression of CD39 on T cells was upregulated through CD3/CD28 stimulation and its blockade by a newly developed nanobody construct resulted in increased proliferation (eFluor), activation (CD25 and CD134), and production of cytotoxic cytokines (IFN-γ, TNF-α, and granzyme-B) of CD8⁺ T cells.

532

项与 CD28 相关的新闻（医药）

2024-10-30

·Insight数据库

CD3 再现重磅交易！自免领域掀起热潮

继 ADC、核药后，CD3 TCE 类药物也迎来了高光时刻，正在自免领域掀起一场热潮。昨天，恩沐生物以 3 亿美元预付款将 CD3/CD19/CD20 三抗授权给 GSK，GSK 将重点关注该药在 B 细胞驱动的自身免疫性疾病的潜力，如系统性红斑狼疮（SLE）和狼疮肾炎（LN），并有可能扩展到相关的自身免疫性疾病。除恩沐生物外，过去几个月，还有 3 款与自免疾病相关的国产 CD3 双抗/三抗成功达成了出海合作：默沙东以 13 亿美元引进同润生物的 CD3/CD19 双抗 CN201； Vignette Bio 以超 6 亿美元引进岸迈生物的 CD3/BCMA 双抗 EMB-06；以及通过 NewCo 模式出海的嘉和生物 CD3/CD20 双抗 GB261。不难预见，CD3 TCE 类药物将以破竹之势席卷自免领域，激发市场探索新型治疗方案的热情。横跨三大疾病市场双抗/三抗/多抗的靶点组合类型丰富，其中尤以 CD3 双抗研发最为火热。目前全球在研的双抗/三抗/多抗靶点分布和药物类型分布截图来源：Insight 数据库这是由于，CD3 与 T 细胞的激活密切相关，通过结合 CD3 和肿瘤相关抗原，能够引导并激活 T 细胞接近并杀伤肿瘤细胞，从而增强治疗效果，而且 CD3 双抗针对适应症广泛，已在血液瘤和实体瘤中验证成药性，如今正在拓展至自身免疫疾病领域。截至目前，全球已获批上市的基于 CD3 靶点的 TCE 有 11 款，均为双抗（包括 Catumaxomab），靶点组合类型包括 CD3×CD19、CD3×CD20、CD3×BCMA 等。全球已获批基于 CD3 靶点的双抗产品数据来源：Insight 数据库具体来看，这 11 种 CD3 双抗主要获批血液瘤，包括多发性骨髓瘤、复发或难治性（R/R）滤泡性淋巴瘤、R/R 弥漫性大 B 细胞淋巴瘤等。不过，也有少部分针对实体瘤，包括 Immunocore 的 CD3/gp100 双抗 Tebentafusp、安进的 CD3/DLL3 双抗 Tarlatamab，分别获批用于治疗黑色素瘤、广泛期小细胞肺癌（ES-SCLC）。一款双抗药物能否获得更高的市场价值，不仅要具备显著的疗效和安全性，还得获批广泛的适应症。市场潜力巨大的自免市场，便是新的突破口。当前，药企正在探索靶向 B 细胞 CD3 TCE 在自免领域的治疗潜力。这是由于，B 细胞驱动的免疫异常是多种自免疾病的核心发病机制，在血液瘤和自免疾病中共同起到关键作用，而且 CD3 亚基的缺陷通常与系统性红斑狼疮等自免疾病相关，CD19 也可作为各种自免疾病的潜在靶点。今年 4 月，Nature Medicine 发表的一篇论文显示，安进的 CD3/CD19 双抗 Blinatumomab（贝林妥欧单抗）在 6 名难治性类风湿关节炎患者的初步数据中显示出积极疗效，为 B 细胞介导的自免疾病的治疗提供了新的策略。 9 月初，《新英格兰医学杂志》发表了两项研究结果：多名难治性自免患者接受强生 CD3/BCMA 双抗 Teclistamab 治疗后病情显著缓解，其中，一名系统性红斑狼疮患者实现了症状完全缓解；4 例自免患者（系统性硬化症、原发性干燥综合征、特发性炎性肌病、类风湿性关节炎）接受 Teclistamab 治疗后疾病活动度皆获得改善。值得一提的是，这些研究还只是 CD3 TCE 在自免领域开辟新战场的「冰山一角」。自免：CD3 TCE 的新战场随着 CD3 双抗在自身免疫疾病中展现出治疗潜力，外资药企开启了「扫货模式」。最近几个月，已有 4 款与自免疾病相关的国产 CD3 TCE 获得了外资药企的青睐： 8 月 5 日，嘉和生物将 CD3/CD20 双抗 GB261 的大中华区外全球权益授权给 TRC 2004，将获得 TRC 2004 数量可观的股权、数千万美元预付款、4.43 亿美元里程碑金额，以及个位数至双位数比例的销售分成，双方的合作将主要集中探索 GB261 在自免疾病方面的潜力； 8 月 9 日，默沙东宣布将通过子公司收购同润生物用于治疗 B 细胞相关疾病的新型 CD3/CD19 双抗 CN201，并将预付 7 亿美元现金获得 CN201 的全部全球权利，以及后续将支付高达 6 亿美元的里程碑付款； 9 月 4 日，Vignette Bio 引进岸迈生物 CD3/BCMA 双抗 EMB-06 在大中华区以外的全球权益，岸迈生物将以现金和 Vignette 股权的形式收取总计 6000 万美元的首付款对价，并将有权收取最多 5.75 亿美元的开发、上市、和商业化的里程碑付款，以及基于净销售额的收入分成。 10 月 29 日，葛兰素史克以 3 亿美元预付获得恩沐生物靶向 CD3/CD19/CD20 三抗 CMG1A46 的全部全球权利。此外，恩沐生物将有资格获得总额 5.5 亿美元的开发和商业里程碑付款。值得一提的是，日前，TRC 2004 公司和 Vignette Bio 公司都已被 Candid Therapeutics 收购。Candid 公司旨在开发能够清除特定 B 淋巴细胞群的 T 细胞连接器（TCE）抗体，拟用于治疗自身免疫疾病。通过本次收购，Candid 获得了上述两款中国公司开发的（ GB261 和 EMB-06）双抗权益。可见，自免疾病领域已成为 CD3 TCE 必须拿下的新战场。 2024 年至今 CD3 TCE 领域发生的相关交易（截至 2024.10.29）图片来源：Insight 数据库目前，嘉和生物已在中国和澳洲完成 GB261 针对 B-NHL（DLBCL 和 FL）进行的 1/2 期多中心研究，结果显示出富有前景的疗效和非常优越的安全性和有效性。GB261 的特性使其成为一种非常有前景的 B 细胞耗竭剂，其适应症潜力超出肿瘤学范围，也适用于患者中有大量未满足医疗需求的各种免疫学和自体免疫适应症。 CN201 正在开展 1 期和 1b/2 期临床试验，分别用于治疗复发或难治性非霍奇金淋巴瘤和复发或难治性 B 细胞急性淋巴细胞白血病。默沙东后续计划评估 CN201 在 B 细胞恶性肿瘤的治疗潜力，并有望用于治疗自免疾病。 EMB-06 是在岸迈生物的 T 细胞接合平台下开发的首个 TCE 分子，目前正在复发或难治的多发性骨髓瘤中进行 1 项 I/II 期研究。岸迈生物的 CEO 和创始人吴辰冰博士表示，「EMB-06 在多发性骨髓瘤病人上的评估中，已经展现出了前景可期的临床药效。我们期待进一步评估 EMB-06 在自身免疾病中的潜力。」 CMG1A46 是一款靶向 CD3/CD19/CD20 三抗，目前正在美国和中国开展针对白血病和淋巴瘤的 I 期临床试验。GSK 计划于 2025 年开始针对狼疮的 I 期临床试验。这意味着，未来若能在自免领域成功验证成药性，CD3 双抗将成为横跨血液瘤、实体瘤和自免三大疾病市场的大药。其他「拓荒者」 CD3 TCE 的火热，不仅体现在 BD 交易频发，还在资本市场掀起了一场狂欢行情。今年 4 月，美股药企 Cullinan 在宣布扩展 CD3/CD19 双抗 CLN-978 在自免疾病中的应用后，当月股价大涨近 60%。可见，市场对该产品在自免疾病中的治疗潜力寄予了厚望。在 2024 年中期业绩报告中，Cullinan 表示仍有望在今年第三季度向 FDA 提交 CLN-978 用于系统性红斑狼疮的 IND 申请，并计划将类风湿性关节炎作为第二个自免适应症。另外，在嘉和生物宣布 CD3/CD20 双抗 GB261 成功出海后，公司股价自 8 月 5 日以来累计大涨超过 50%。 CD3 TCE 展现出的大药潜质，吸引了安进、强生、默沙东等跨国制药巨头抢滩布局。更重要的是，「拓荒者」远不止于此。根据 Insight 数据库，目前全球共有 20 款左右处于活跃状态的 CD3 双抗开展了针对自免疾病的临床研究，靶点组合类型主要集中在 CD3×CD19、CD3×CD20、CD3×BCMA。全球在研的针对自免疾病的 CD3 双抗图片来源：Insight 数据库而处于活跃状态的 CD3 的三抗/多抗目前只有 5 款开展了针对自免疾病的研究。全球在研的针对自免疾病的 CD3 三抗/多抗图片来源：Insight 数据库国内药企方面，除了已经达成出海合作的 4 家药企外，布局者还有神州细胞、德琪医药、恒瑞医药、和铂医药等。不过从临床进度看，大多数针对自免疾病的国产 CD3 TCE 仍处于早期临床前阶段。 9 月 10 日，神州细胞的 CD3/CD20 双抗 SCTB35 获 NMPA 批准开展临床，适应症为 B 细胞介导的自身免疫性疾病；德琪医药 CD3/CD19 双抗 ATG-201 主要针对 B 细胞相关的自免疾病，目前正处于临床前阶段。 8 月 8 日，惠和生物靶向 CD19/CD28/CD3 的三抗 CC312 获批临床，用于系统性红斑狼疮； 4 月 29 日，天劢源和靶向 CD19/CD3 的双抗 A-319 在中国启动 I 期临床（NCT06400537），用于系统性红斑狼疮。结语当下，自免双抗/三抗/多抗正日益成为新药研发的焦点，尤其在能够跨越血液瘤、实体瘤和自免疾病这三大广阔版图的 CD3 TCE 身上，我们看到了其作为潜力大药的无限可能。展望未来，CD3 TCE 的故事无疑将更加精彩纷呈。封面来源：站酷海洛 Plus 免责声明：本文仅作信息分享，不代表 Insight 立场和观点，也不作治疗方案推荐和介绍。如有需求，请咨询和联系正规医疗机构。编辑：vvy PR 稿对接：微信 insightxb 投稿：微信 insightxb；邮箱 insight@dxy.cn 多样化功能、可溯源数据…… Insight 数据库网页版等你体验点击阅读原文，立刻解锁！

抗体药物偶联物引进/卖出临床申请

2024-10-30

·医药笔记

自免热潮下：逆势翻盘的biotech们

▎Armstrong 近两年来MNC纷纷扫货自免产品，包括单抗、双抗、TCE、CAR-T等，这股热潮也蔓延至资本市场，一些历经波折的biotech有了逆风翻盘的机会。 Alpine Alpine Immune成立于2015年，早期核心管线为CD28/ICOS拮抗剂，但临床开发并不顺利，肿瘤管线同样推进不顺利。最近几年，Alpine的核心管线才转为TACI-Fc融合蛋白Povetacicept，今年即将推进到三期临床。 Alpine Immune的市值长期徘徊在10亿美元左右，伴随着自免风口的到来，今年4月，Vertex以49亿美元收购Alpine。 TCE：Cullinan、同润生物、恩沐生物 TCE领域的B细胞靶向CD3双抗，原本主要用于血液瘤，在资本市场上关注度并不高。随着CD19 CAR-T在自免领域的开拓性探索，行业开始高度关注TCE在自免领域的潜力。Cullinan Oncology的核心管线CD3/CD19双抗，率先在今年4月宣布转战自免赛道，并很快完成2.8亿美元增发募资。同时，Cullinan Oncology将名字也直接改成了Cullinan Therapeutics。同润生物的首发管线同样为CD3/CD19双抗CN201，同润生物在2018年完成1.5亿美元A轮融资，此后未再融过资。今年8月，默沙东以7亿美元引进同润生物的CN201。根据CN201今年ASCO会议上汇报了血液瘤的一期临床数据，其中5mg以上剂量对于FL/MCL/MZL/SLL的ORR达到100%。安全性方面，CRS发生率为7%，且均为1级或2级，同时没有神经毒性。恩沐生物成立于2016年，首发管线CMG1A46为一款CD3/CD19/CD20三抗，如今推进到血液瘤一期临床阶段。恩沐生物的融资并不算顺利，2021年A+轮融资后，与博锐生物做过一次授权合作，此后近三年无新的融资。前不久，恩沐生物完成主流美元基金Foresite Capital的新一轮融资，并一起推动了昨日与葛兰素史克的授权合作，后者以3亿美元预付款+5.5亿美元的价格引进了CMG1A46的全球权益。总结虽然自免风口带来了新的机会，但也要看到真正实现逆风翻盘的，还是那些分子设计上具有显著差异化优势，并且经过初步临床验证的biotech。Alpine的Povetacicept亲和力远高于Vera的Atacicept和荣昌生物的泰它西普，并经过二期临床验证。同润生物的CN201安全性优势显著，且B细胞淋巴瘤疗效显著。恩沐生物的CMG1A46同时覆盖CD19、CD20两个经过验证的B细胞靶点，且为活性更强的2+1价态设计。 Armstrong技术全梳理系列 GPRC5D靶点全梳理； CD40靶点全梳理； CD47靶点全梳理；补体靶向药物技术全梳理；补体药物：眼科治疗的重要方向； Claudin 6靶点全梳理； Claudin 18.2靶点全梳理；靶点冷暖，行业自知；中国大分子新药研发格局；被炮轰的“me too”；佐剂百年史；胰岛素百年传奇； CUSBEA：风雨四十载；中国新药研发的焦虑；中国生物医药企业的研发竞争；中国双抗竞争格局；中国ADC竞争格局；中国双抗技术全梳理；中国ADC技术全梳理； Ambrx技术全梳理； Vir Biotech技术全梳理； Immune-Onc技术全梳理；亘喜生物技术全梳理；康哲药业技术全梳理；科济药业技术全梳理；恺佧生物技术全梳理；同宜医药技术全梳理；百奥赛图技术全梳理；腾盛博药技术全梳理；创胜集团技术全梳理；永泰生物技术全梳理；中国抗体技术全梳理；德琪医药技术全梳理；德琪医药技术全梳理2.0；和铂医药技术全梳理；荣昌生物技术全梳理；再鼎医药技术全梳理；药明生物技术全梳理；恒瑞医药技术全梳理；豪森药业技术全梳理；正大天晴技术全梳理；吉凯基因技术全梳理；基石药业技术全梳理；百济神州技术全梳理；百济神州技术全梳理第2版；信达生物技术全梳理；信达生物技术全梳理第2版；中山康方技术全梳理；复宏汉霖技术全梳理；先声药业技术全梳理；君实生物技术全梳理；嘉和生物技术全梳理；志道生物技术全梳理；道尔生物技术全梳理；尚健生物技术全梳理；康宁杰瑞技术全梳理；科望医药技术全梳理；科望医药技术全梳理2.0；岸迈生物技术全梳理；礼进生物技术全梳理；康桥资本技术全梳理；余国良的抗体药布局；荃信生物技术全梳理；安源医药技术全梳理；三生国健技术全梳理；仁会生物技术全梳理；乐普生物技术全梳理；同润生物技术全梳理；宜明昂科技术全梳理；派格生物技术全梳理；迈威生物技术全梳理； Momenta技术全梳理； NGM技术全梳理；普米斯生物技术全梳理；普米斯生物技术全梳理2.0；三叶草生物技术全梳理；贝达药业抗体药全梳理；泽璟制药抗体药全梳理；恒瑞医药抗体药全梳理；齐鲁制药抗体药全梳理；石药集团抗体药全梳理；豪森药业抗体药全梳理；华海药业抗体药全梳理；科伦药业抗体药全梳理；百奥泰技术全梳理；凡恩世技术全梳理。

并购免疫疗法临床1期引进/卖出细胞疗法

2024-10-29

·PRNewswire

Biond Biologics Announces Clinical Trial Collaboration and Supply Agreement with Merck KGaA, Darmstadt, Germany to Evaluate BND-35 in Combination with Cetuximab in a Phase 1 Clinical Study in Patients with Solid Tumors

MISGAV, Israel, Oct. 29, 2024 /PRNewswire/ -- Biond Biologics Ltd. ("Biond" or the "Company"), is a private clinical-stage biopharmaceutical company focusing on novel immunotherapies for cancer and innovative platforms for the intracellular delivery of biologics. Biond is pleased to announce a clinical trial collaboration and supply agreement with Merck KGaA, Darmstadt, Germany, to evaluate its immunotherapy agent BND-35 in combination with Merck KGaA, Darmstadt, Germany's anti-EGFR monoclonal antibody cetuximab (Erbitux®) in a Phase 1 clinical trial (BND-35-001, NCT06274437) for the treatment of patients with unresectable or metastatic solid tumors. Under the terms of this agreement, Merck KGaA, Darmstadt, Germany will supply Biond Biologics with cetuximab to support Biond's Phase 1 clinical trial, aimed at evaluating the safety and efficacy of BND-35 in combination with cetuximab. Enrollment to the BND-35 dose-escalation monotherapy arm has already begun and several patients have already been dosed. BND-35 is a novel anti-ILT3 (LILRB4) antibody that inhibits the interaction between ILT3 and various extracellular matrix ligands, including fibronectin, a major component of many tumor microenvironments (TME). ILT3 is expressed on myeloid suppressive cells and contributes to a pro-tumorigenic TME. Additionally, ILT3 reduces the effectiveness of targeted antibody therapies that leverage antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP), immunological mechanisms known to eliminate tumor cells. BND-35 reprograms the suppressive TME to a more pro-inflammatory one and reverses the inhibitory effects of ILT3 on ADCC and ADCP mechanisms. "We are thrilled to partner with Merck KGaA, Darmstadt, Germany to secure the supply of cetuximab for our clinical trial and thank Merck KGaA, Darmstadt, Germany for their interest in BND-35" said Tal Sines, VP of Business Development at Biond Biologics. "Our preclinical data show that BND-35 can synergize with therapies such as cetuximab, that promote ADCC and ADCP activities. It could provide a potential new treatment option for patients with solid tumors. About BND-35 BND-35, an innovative anti-ILT3/LILRB4 antibody designed to remodel the tumor microenvironment. BND-35 is currently under evaluation as a monotherapy in a Phase 1 clinical trial, which is exploring the safety, tolerability, and potential anti-tumor activity of BND-35 (NCT06274437). BND-35 is being assessed as monotherapy in the BND-35-001 trial, and in combination with established anti-EGFR (cetuximab) and PD-L1 therapies across various indications. About Biond Biologics Biond Biologics stands at the cutting edge of innovative therapies that target novel oncology pathways and enable the intracellular delivery of biologics. The company is dedicated to leverage advanced science and pioneering technologies into transformative drugs for diseases with significant unmet medical needs. Biond Biologics actively seeks synergistic collaborations with leading biopharmaceutical entities to bring novel medicines to patients worldwide. The company's robust pipeline also includes BND-22 (SAR444881), a groundbreaking first-in-class ILT2-blocking antibody in partnership with Sanofi, and BND-67, targeting CD28 shedding, a newly discovered immune evasion mechanism. Additionally, Biond is advancing INspire, a revolutionary platform for the intracellular delivery of protein therapeutics, including antibodies, proteins, or enzymes into cells. Media Contact: Tal Sines VP of Business Development Biond Biologics Ltd. +972-4 884 4337 [email protected] SOURCE Biond Biologics Ltd. WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED