Precision Biologics将在2025年AACR年会上展示利用单克隆抗体（mAb）PB-223的新型抗体药物偶联物（ADC）的最新数据-动脉网

Precision Biologics to Present Recent Data on a New Antibody-Drug Conjugate (ADC) Utilizing the Monoclonal Antibody (mAb) PB-223, at AACR Annual Meeting 2025

CISION 等信源发布 2025-04-25 21:18

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BETHESDA, Md.

贝塞斯达，马里兰州

，

April 25, 2025

2025年4月25日

/PRNewswire/ -- Precision Biologics, Inc. reports preclinical development and characterization of a novel ADC using its anti-core 2 O-glycans anti-human carcinoma mAb PB-223 will be presented in a poster at the American Association for Cancer Research (AACR) Annual Meeting 2025, on

/PRNewswire/ -- Precision Biologics, Inc. 报告了其使用抗核心2型O-聚糖的抗人类癌单克隆抗体PB-223开发和表征一种新型抗体药物偶联物（ADC）的临床前研究，该研究将在2025年美国癌症研究协会（AACR）年会上以海报形式展示。

April 29

4月29日

, 2025, McCormick Place Convention Center,

，2025年，麦考密克会展中心，

Chicago, IL

伊利诺伊州芝加哥

, USA.

，美国。

Poster title

海报标题

: Development and characterization of an antibody-drug conjugate (ADC) utilizing PB-223, a novel monoclonal antibody (mAb) specifically targeting core 2 O-glycans on human carcinomas

利用PB-223（一种新型单克隆抗体（mAb），专门靶向人类癌细胞上的核心2型O-聚糖）开发和表征抗体药物偶联物（ADC）。

The presentation of the poster will be made in person on the following date and location:

海报展示将于以下日期和地点亲自进行：

April 29

4月29日

, 2025,

，2025，

9am-12pm

上午9点至中午12点

McCormick Place Convention Center,

麦考密克会展中心，

Chicago, IL

伊利诺伊州芝加哥市

, USA

，美国

Session Title: Antibodies and Antibody-Drug Conjugates

会议标题：抗体与抗体药物偶联物

Poster Section 36

海报部分36

Abstract Control Number 2878

抽象控制号 2878

BACKGROUND:

背景：

Antibody-drug conjugates (ADCs) represent a cutting-edge approach in cancer therapy. The three essential components of an ADC include: the mAb, the linker, and the cytotoxic payload. The mAb in current ADCs is usually designated to target specific tumor-associated antigens that are overexpressed on the surface of cancer cells..

抗体药物偶联物（ADC）代表了癌症治疗中的一种前沿方法。ADC的三个基本组成部分包括：单克隆抗体（mAb）、连接子和细胞毒性载荷。当前ADC中的单克隆抗体通常旨在靶向在癌细胞表面过度表达的特定肿瘤相关抗原。

Our ADC contains the following components:

我们的ADC包含以下组件：

The mAb:

单克隆抗体：

We used PB-223, an innovative mAb developed through affinity maturation of mAb NEO-102 (Ensituximab), a chimeric human IgG1 mAb that targets truncated core 2 O-glycans, specifically expressed by cancer cells and not by healthy tissues. The binding affinity of PB-223 for its target was improved, compared to NEO-102, by optimizing its VH and VL sequences through Fast Screening for Expression Biophysical Properties and Affinity.

我们使用了PB-223，这是一种通过对抗体NEO-102（Ensituximab）进行亲和力成熟而开发的创新单克隆抗体。NEO-102是一种嵌合的人类IgG1单克隆抗体，靶向截短的core 2型O-聚糖，这种聚糖特异性地在癌细胞中表达，而不在健康组织中表达。与NEO-102相比，PB-223对其靶标的结合亲和力通过优化其VH和VL序列得到了提高，该优化过程采用了快速筛选表达生物物理特性和亲和力的方法。

PB-223 demonstrated a binding affinity (KD) at least 4-fold lower than NEO-102, indicating stronger tumor binding. An immunohistochemistry analysis also revealed that PB-223 binds to a wider spectrum of tumor tissues compared to NEO-102, including not only colorectal, and pancreatic cancer, but also triple negative breast, prostate, kidney, head and neck, liver, and bladder cancer.

PB-223 展示出比 NEO-102 至少低 4 倍的结合亲和力 (KD)，表明其具有更强的肿瘤结合能力。免疫组织化学分析还显示，PB-223 能够比 NEO-102 结合更广泛的肿瘤组织，不仅包括结直肠癌和胰腺癌，还包括三阴性乳腺癌、前列腺癌、肾癌、头颈部癌、肝癌以及膀胱癌。

Further experiments show PB-223 does not bind to normal tissues and that it can be internalized into human cancer cell lines expressing its target..

进一步的实验表明，PB-223不与正常组织结合，并且可以内化到表达其靶标的癌细胞系中。

The payload:

有效载荷：

Monomethyl auristatin E (MMAE) was used as payload. MMAE is a potent antimitotic agent that inhibits cell division by blocking the polymerization of tubulin and is the most common ADC payload used to be linked to antibodies in clinical development for oncologic applications.

单甲基澳瑞他汀E（MMAE）被用作载荷。MMAE是一种强效的抗有丝分裂剂，通过阻断微管蛋白的聚合来抑制细胞分裂，是目前临床开发中用于肿瘤学应用中最常见的与抗体连接的ADC载荷。

The linker:

链接器：

mc-vc-PABc was used as linker. PB-223 was conjugated to the linker-payload through a cysteine-based conjugation method.

mc-vc-PABc 被用作连接子。PB-223 通过基于半胱氨酸的结合方法与连接子载荷结合。

STUDY PRESENTED AT AACR 2025

研究发布于AACR 2025

：

After development of the ADC we proceeded with its characterization, evaluating the following features:

在开发ADC后，我们继续对其进行特性分析，评估以下特性：

DAR:

显示宽高比：

The drug-to-antibody ratio (DAR) is crucial to predict the efficacy and safety of ADCs. It is generally believed that a DAR between 2 and 4 is the best choice for ADC drugs. Higher DAR may disrupt the pharmacokinetic properties of ADCs, while lower DAR significantly negatively affects the potency of ADCs.

药物抗体比（DAR）对于预测ADC的疗效和安全性至关重要。一般认为，DAR在2到4之间是ADC药物的最佳选择。较高的DAR可能会破坏ADC的药代动力学特性，而较低的DAR则会显著负面影响ADC的效力。

We developed three ADCs: PB-MMAE-2, PB-MMAE-5 and PB-MMAE-6. .

我们开发了三种ADC：PB-MMAE-2、PB-MMAE-5和PB-MMAE-6。

The DAR for these ADCs was 3.72, 3.92 and 4.15, respectively.

这些ADC的DAR分别为3.72、3.92和4.15。

Binding of ADCs to cancer cells expressing core 2 O-glycans:

ADCs与表达核心2 O-聚糖的癌细胞结合：

flow cytometry was used for binding assessment of three ADC clones using the human ovarian cancer cell line OV-90 as the target.

使用流式细胞术评估了三个ADC克隆与人卵巢癌细胞系OV-90作为靶标的结合情况。

All three ADCs exhibit similar binding affinity to OV-90 compared to PB-223.

所有三种ADC与PB-223相比，对OV-90表现出相似的结合亲和力。

Killing of cancer cells:

杀死癌细胞：

We evaluated the ability of all three ADC clones to kill OV-90 cells.

我们评估了所有三种ADC克隆杀死OV-90细胞的能力。

All three ADCs effectively killed OV-90 cells (80% of cells were dead 5 days after treatment)

所有三种ADC有效杀死了OV-90细胞（治疗5天后80%的细胞死亡）。

. We then chose one ADC clone, PB-MMAE-5, to test its ability to kill additional human cancer cell lines.

我们随后选择了一个ADC克隆，PB-MMAE-5，来测试其杀死其他人类癌细胞系的能力。

Preliminary results show that PB-MMAE-5 can kill human prostate, triple positive and triple negative breast, lung, colon, pancreatic cancer cell lines.

初步结果显示，PB-MMAE-5可以杀死人类前列腺、三阳性乳腺癌、三阴性乳腺癌、肺癌、结肠癌和胰腺癌细胞系。

Safety in vivo:

体内安全性：

We chose the ADC clone PB-MMAE-5 to test its toxicity in rats. The ADC PB-vcMMAE-5 in rats was administered intravenously at a concentration of 2.3 mg/kg as single dose. Animal body weight was measured at different time points until 14 days after ADC administration.

我们选择了ADC克隆PB-MMAE-5来测试其在大鼠中的毒性。ADC PB-vcMMAE-5以2.3 mg/kg的浓度单次静脉注射给药。在ADC给药后14天内，不同时间点测量了动物体重。

The ADC PB-vcMMAE-5 was well tolerated in rats. No sign of distress nor loss of body weight were observed after administration.

ADC PB-vcMMAE-5 在大鼠中耐受性良好。给药后未观察到痛苦迹象或体重减轻。

Stability in human plasma:

在人血浆中的稳定性：

Stability of the ADC PB-vcMMAE-5 was evaluated in human plasma. PB-vcMMAE-5 ADC was incubated with male and female human plasma at concentration of 50 µg/mL and 100 µg/mL. Concentration in human plasma was detected by ELISA at 0h, 24h (1 day), 48h (2 days), 96h (4 days), 168h (7 days), 240h (10 days), 336h (14 days).

在人血浆中评估了ADC PB-vcMMAE-5的稳定性。将PB-vcMMAE-5 ADC以50 µg/mL和100 µg/mL的浓度与男性和女性的人血浆一起孵育。通过ELISA在0小时、24小时（1天）、48小时（2天）、96小时（4天）、168小时（7天）、240小时（10天）、336小时（14天）检测人血浆中的浓度。

。

The ADC was stable in human plasma

ADC在人血浆中稳定。

(after 14 days, mean residual rate of PB-vcMMAE-5 ADC in human plasma was 23% for ADC at 100 µg/mL and 22% for ADC at 50 µg/mL).

（14天后，PB-vcMMAE-5 ADC在人血浆中的平均残留率在ADC浓度为100 µg/mL时为23%，在ADC浓度为50 µg/mL时为22%）。

Efficacy in vivo:

体内功效：

The efficacy of the ADC PB-vcMMAE-5 was assessed in OV-90 subcutaneous xenograft model established in NOD-SCID mice. The ADC PB-vcMMAE-5 was administered intravenously at doses 1 mg/kg and 3 mg/kg, once per week for three weeks.

在NOD-SCID小鼠建立的OV-90皮下异种移植模型中评估了ADC PB-vcMMAE-5的疗效。ADC PB-vcMMAE-5以1 mg/kg和3 mg/kg的剂量静脉注射，每周一次，持续三周。

Preliminary data suggest that PB-vcMMAE-5 exhibits anti-tumor activity in the NOD-SCID mice tumor model.

初步数据显示，PB-vcMMAE-5在NOD-SCID小鼠肿瘤模型中表现出抗肿瘤活性。

Two days after the second dose of PB-vcMMAE-5 at 3mg/kg, treated mice showed a significant reduction in tumor volume compared to mice treated with an 1mg/kg dose of PB-vcMMAE-5, PBS or payload alone.

在给予3mg/kg的PB-vcMMAE-5第二剂后的两天，与使用1mg/kg剂量的PB-vcMMAE-5、PBS或单独使用有效载荷处理的小鼠相比，治疗组小鼠的肿瘤体积显著减少。

Findings from this study showed that PB-vcMMAE-5 can kill cancer cells expressing PB-223's target, is not toxic, is effective in vivo, and is stable in human plasma, suggesting that PB-vcMMAE-5 has promising potential as a therapeutic option for a range of human malignancies expressing core 2 O-glycans..

本研究的结果表明，PB-vcMMAE-5可以杀死表达PB-223靶标的癌细胞，无毒性，在体内有效，并且在人血浆中稳定，这表明PB-vcMMAE-5作为一种治疗表达核心2型O-聚糖的多种人类恶性肿瘤的潜在治疗选择具有良好的前景。

The PDF of the poster will be available starting from

海报的PDF将从以下时间开始提供

April 25, 2025

2025年4月25日

, at the following link:

，通过以下链接：

https://precision-biologics.com/wp-content/uploads/AACR-2025-POSTER.pdf

SOURCE Precision Biologics

来源精密生物公司

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