A Phase Two Study Evaluating Two Doses of Leronlimab (Pro 140) In Combination With Trifluridine + Tipiracil (TAS-102) + Bevacizumab in Participants With CCR5+, Microsatellite Stable (MSS), Relapsed Refractory Metastatic Colorectal Cancer (mCRC)

This is an open label, randomized, two arm, multi-center study to explore the effect of leronlimab on the overall response rate/ overall survival and safety and tolerability when used in combination with trifluridine and tipiracil + bevacizumab in patients with CCR5+, MSS, mCRC who have progressed on prior treatment before participating in the study. The main questions this study aims to answer are:
1. Can leronlimab, in combination with standard of care therapies trifluridine and tipiracil+ bevacizumab, increase the objective response rate in persons with CCR5+, MSS, mCRC who have progressed on prior treatment before participating in the study.
2. Is leronlimab safe and well tolerated in these subjects when used in combination with standard of care therapies trifluridine and tipiracil+ bevacizumab.

开始日期2025-05-30

申办/合作机构

CytoDyn, Inc.

[+1]

NCT05730673

/ Withdrawn临床2期

A Phase II Study of Leronlimab (PRO 140) in Combination With Regorafenib in Patients With CCR5+, Microsatellite Stable (MSS), Metastatic Colorectal Cancer (mCRC)

This is aPhase II Study of Leronlimab (PRO 140) in combination with Regorafenib in Patients with CCR5+, Microsatellite Stable (MSS), Metastatic Colorectal Cancer (mCRC)

开始日期2022-09-20

申办/合作机构

CytoDyn, Inc.

[+1]

NCT04901689

/ Suspended临床3期IIT

A Phase 3, Randomized, Double Blind, Placebo Controlled Trial to Evaluate the Efficacy and Safety of Leronlimab in Combination With Standard of Care for Patients With Coronavirus Disease 2019 (COVID-19) With Need for Mechanical Ventilation or Extracorporeal Membrane Oxygenation

Leronlimab (PRO 140) is a humanized IgG4,k monoclonal antibody (mAb) that recognizes the C-C chemokine receptor type 5 (CCR5). Disruption of the C-C chemokine ligand 5 (CCL5)-CCR5 axis via leronlimab-mediated CCR5 blockade might prevent pulmonary trafficking of pro-inflammatory leukocytes and dampen pathogenic immune activation in coronavirus disease 2019 (COVID-19).
The purpose of the study is to assess the safety and efficacy of leronlimab plus standard of care in critically ill patients hospitalized with COVID-19 pneumonia who are requiring mechanical ventilation or extracorporeal oxigenation (ECMO).

开始日期2021-10-23

申办/合作机构

Hospital Israelita Albert Einstein

[+1]

100 项与 Leronlimab 相关的临床结果

登录后查看更多信息

100 项与 Leronlimab 相关的转化医学

登录后查看更多信息

100 项与 Leronlimab 相关的专利（医药）

登录后查看更多信息

项与 Leronlimab 相关的文献（医药）

2025-06-01·JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES

Leronlimab Treatment for Multidrug-Resistant HIV-1 (OPTIMIZE): A Randomized, Double-Blind, Placebo-Controlled Trial

Article

作者: Dejesus, Edwin ; Hansen, Scott G. ; Sanchez, William E. ; Gathe, Joseph C. ; Meidling, Joseph ; Lalezari, Jacob P. ; Sacha, Jonah B. ; Krishen, Alok ; Ramgopal, Moti N. ; Rolle, Charlotte-Paige ; Yang, Otto O.

Background::

Leronlimab is a humanized κ-IgG4 monoclonal antibody that blocks C–C chemokine receptor type 5. We investigated leronlimab as a treatment option for people living with multidrug-resistant HIV-1.

Setting and Methods::

In a phase 2b/3, multicenter, randomized, double-blind, placebo-controlled study conducted in 21 hospital centers in the United States, treatment-experienced people living with HIV with documented drug resistance were randomly assigned once weekly leronlimab (350 mg subcutaneously) or matching placebo for 1 week overlapping existing failing antiretroviral therapy, followed by a 24-week single-arm extension with weekly leronlimab combined with a new optimized background treatment. The primary end point was achieving ≥0.5 log10 reduction in plasma HIV-1 RNA from baseline at the end of the 1-week double-blinded treatment period.

Results::

Fifty-two participants were enrolled (25 leronlimab and 27 placebo). After the 1-week randomized phase, by the intent-to-treat analysis, 64.0% (16/25) receiving leronlimab achieved ≥0.5 log10 reduction in plasma HIV-1 RNA versus 23.1% (6/26) receiving placebo (P = 0.0032), whereas by per protocol analysis, 72.7% (16/22) receiving leronlimab achieved ≥0.5 log10 reduction in plasma HIV-1 RNA versus 24.0% (6/25) receiving placebo (P = 0.0008). Leronlimab was generally well tolerated with no drug-related serious adverse events reported. Overall, 175 adverse events were reported by 34/52 participants, with 120 (68.6%) adverse events categorized as mild.

Conclusions::

Leronlimab resulted in significantly reduced plasma HIV-1 within 1 week after addition to failing antiretroviral therapy. After 24 weeks combined with an optimized background treatment, most participants had plasma HIV-1 RNA levels <50 copies per milliliter plasma, suggesting utility of leronlimab as a component of salvage therapy.

2025-04-15·JOURNAL OF VIROLOGY

Addition of a short HIV-1 fusion-inhibitory peptide to PRO 140 antibody dramatically increases its antiviral breadth and potency

Article

作者: Gao, Yue ; Zhu, Yuanmei ; Chen, Yue ; Su, Bin ; Gong, Yani ; Chong, Huihui ; Yan, Hongxia ; Li, Li ; He, Yuxian

ABSTRACT:

PRO 140, a humanized anti-HIV monoclonal antibody targeting the cell coreceptor CCR5, is currently under clinical trials, but it only affects CCR5-tropic viruses. In this study, we have engineered two tandem fusion proteins (2P23-PRO140SC and 2P23-PRO140-Fc) with bifunctional activity by adding short fusion-inhibitory peptide 2P23 to the single-chain fragment variable (scFv) of PRO 140 (PRO140SC) with or without the Fc domain of human IgG4. We first demonstrated that 2P23-PRO140SC and 2P23-PRO140-Fc could efficiently bind to the cell membranes through CCR5 anchoring, which did not affect the expression level of CCR5 on the cell surface. We then verified that the addition of 2P23 peptide to PRO140SC enabled a very potent activity against CXCR4-tropic HIV-1 isolates. As expected, the bispecific fusion proteins exhibited highly potent activities in inhibiting divergent HIV-1 subtypes and viral mutants that were resistant to the fusion inhibitors 2P23 and T20, and they displayed relatively low in vitro cytotoxicity. Furthermore, both the fusion proteins had robust in vivo anti-HIV activities in rats, with 2P23-PRO140-Fc much better than 2P23-PRO140SC. In conclusion, our studies have provided bispecific HIV-1 inhibitors that overcome the drawbacks of PRO 140 antibody and offered novel tools for studying the mechanisms of HIV-1 infection.

IMPORTANCE:

Given that HIV-1 evolves with high variability and drug resistance, the development of novel antivirals is important. CCR5-directed antibody PRO 140 is currently under clinical trials, but it only inhibits CCR5-tropic HIV-1 isolates. The designed fusion proteins by adding a minimum fusion-inhibitory peptide to PRO 140 enable dramatically increased activities in inhibiting both CCR5-tropic and CXCR4-tropic viruses, thus offering novel antiviral agents with a bispecific functionality that can overcome the drawbacks of PRO 140 antibody.

2024-12-31·mAbs

FcRn-enhancing mutations lead to increased and prolonged levels of the HIV CCR5-blocking monoclonal antibody leronlimab in the fetuses and newborns of pregnant rhesus macaques

Article

作者: Zikos, Joanna ; Shaqra, Ala M ; Usachenko, Jodie L ; Schiffer, Celia A ; Wu, Helen L ; Reed, Jason S ; Van Rompay, Koen K A ; Magnani, Diogo M ; Sacha, Jonah B ; Watanabe, Jennifer ; Webb, Gabriela M

Prenatal administration of monoclonal antibodies (mAbs) is a strategy that could be exploited to prevent viral infections during pregnancy and early life. To reach protective levels in fetuses, mAbs must be transported across the placenta, a selective barrier that actively and specifically promotes the transfer of antibodies (Abs) into the fetus through the neonatal Fc receptor (FcRn). Because FcRn also regulates Ab half-life, Fc mutations like the M428L/N434S, commonly known as LS mutations, and others have been developed to enhance binding affinity to FcRn and improve drug pharmacokinetics. We hypothesized that these FcRn-enhancing mutations could similarly affect the delivery of therapeutic Abs to the fetus. To test this hypothesis, we measured the transplacental transfer of leronlimab, an anti-CCR5 mAb, in clinical development for preventing HIV infections, using pregnant rhesus macaques to model in utero mAb transfer. We also generated a stabilized and FcRn-enhanced form of leronlimab, termed leronlimab-PLS. Leronlimab-PLS maintained higher levels within the maternal compartment while also reaching higher mAb levels in the fetus and newborn circulation. Further, a single dose of leronlimab-PLS led to complete CCR5 receptor occupancy in mothers and newborns for almost a month after birth. These findings support the optimization of FcRn interactions in mAb therapies designed for administration during pregnancy.

149

项与 Leronlimab 相关的新闻（医药）

2025-04-29

·GlobeNewswire-Health Care

CytoDyn Leadership Team To Attend ESMO Breast Cancer Meeting in Munich, Germany

Dr. Jacob Lalezari, CEO, and Dr. Richard Pestell, Lead Consultant in Preclinical and Clinical Oncology, to lead CytoDyn group in attendance VANCOUVER, Washington, April 29, 2025 (GLOBE NEWSWIRE) -- CytoDyn Inc. (OTCQB: CYDY) ("CytoDyn" or the "Company"), a biotechnology company developing leronlimab, a CCR5 antagonist with the potential for multiple therapeutic indications, is pleased to announce that the Company will be presenting a poster at the upcoming European Society for Medical Oncology’s (“ESMO”) Breast Cancer meeting, following its promising survival observations among patients with metastatic triple-negative breast cancer (“mTNBC”) treated with leronlimab. The conference will take place on May 14-17, 2025, in Munich, Germany, and CytoDyn’s presentation is scheduled for May 15, 2025. As announced in February 2025, a review of patients treated with leronlimab during CytoDyn’s prior clinical trials in oncology revealed observed survival rates at 12, 24, and 36 months that compare favorably to expected outcomes with currently approved therapies. The Company has also now confirmed survival outcomes in a group of patients with mTNBC and four prior lines of treatment who are alive more than 48 months after receiving leronlimab. This includes four patients who currently identify as having no evidence of ongoing disease and a fifth patient who is alive with stable disease. CytoDyn has already initiated a follow-up protocol to continue to monitor these surviving patients into the future. “We look forward to sharing details on the progress we have made advancing our clinical development pipeline for leronlimab in oncology,” said Dr. Lalezari. “We are also excited to share information about the apparent mechanism of action in long-term surviving patients that we see as a potentially paradigm-shifting development in solid tumor oncology.” Dr. Lalezari will be joined at the conference by Dr. Richard Pestell, MD, PhD, AO, Lead Consultant in Preclinical and Clinical Oncology, who will present during the poster display session in Hall B0 on Thursday, May 15 from 12:00-12:45PM CEST. Several other CytoDyn key opinion leaders will also be attending the conference. About CytoDyn CytoDyn is a clinical-stage biotechnology company focused on the development and commercialization of leronlimab, an investigational humanized IgG4 monoclonal antibody (mAb) that is designed to bind to C-C chemokine receptor type 5 (CCR5), a protein on the surface of certain immune system cells that is believed to play a role in numerous disease processes. CytoDyn has studied leronlimab in multiple therapeutic areas, including oncology, infectious disease, and autoimmune conditions. Note Regarding Forward-Looking Statements This news release contains forward-looking statements relating to, among other things, product development, market position, future operating and financial performance, and business strategy. The reader is cautioned not to rely on these statements, which are based on current expectations of future events. For important information about these statements and our Company, including the risks, uncertainties and other factors that could cause actual results to vary materially from the assumptions, expectations and projections expressed in any forward-looking statements, the reader should review our Annual Report on Form 10-K for the fiscal year ended May 31, 2024, including the section captioned “Forward-Looking Statements” and Item 1A Risk Factors, and our Quarterly Report on Form 10-Q for the fiscal quarter ended February 28, 2025. CytoDyn Inc. does not undertake to update any forward-looking statement as a result of new information or future events or developments. Media Contacts CytoDynRiyaz LalaniGagnier CommunicationsCytoDyn@gagnierfc.com

ASCO会议

2025-03-27

·小药说药

肿瘤免疫治疗中的趋化因子：解码微环境中的“导航信号”

-01- 引言趋化因子是负责免疫细胞运输和淋巴组织发育的细胞因子亚家族。目前，据报道有50种不同的趋化因子，根据其主要蛋白质结构的前两个半胱氨酸（C）残基的位置，可分为四大类，即C、CC、CXC和CX3C趋化因子。每个免疫细胞亚群都有不同的趋化因子受体表达模式，这使得它们对趋化因子有不同的反应，并根据每个环境的特殊需要迁移。在癌症中，它们在免疫细胞迁移到肿瘤中的模式中起着关键作用，从而形成肿瘤微环境的免疫特征，通常朝向促肿瘤形成状态。此外，趋化因子可以直接靶向肿瘤微环境中的非免疫细胞，包括肿瘤细胞、基质细胞和血管内皮细胞。因此，趋化因子参与多种癌症发展过程，如血管生成、转移、癌细胞增殖、干性和侵袭性，是疾病进展的关键决定因素，对患者预后和治疗反应有很大影响。由于它们在癌细胞和免疫浸润细胞中重要的调节功能，使得趋化因子配体及其受体成为非常强大的治疗靶点。 -02- 一、趋化因子在肿瘤免疫中的作用免疫逃避和免疫抑制细胞的募集趋化因子在引导免疫细胞迁移中起着至关重要的作用，而免疫细胞迁移是启动和传递有效的抗肿瘤免疫反应所必需的。TME中的趋化因子分泌通常会发生改变，异常的趋化因子分布可促进免疫抑制的促肿瘤细胞（即Treg细胞、MDSC和TAM）分化和浸润到肿瘤中。 Treg细胞的趋化因子受体CCR4的表达高于其他CD4+T细胞，其响应CCL22，一种由TAM和原发肿瘤细胞产生的趋化因子。除了CCR4外，Treg细胞还可以表达其他能够介导其浸润TME的趋化因子受体，如CCR5或CCR10，其配体CCL28存在于TME的缺氧区域。巨噬细胞主要通过CCL2–CCR2信号通路招募到TME中。CCL2的肿瘤表达与许多肿瘤中TAM的数量相关，并且通常与患者预后不良相关。与Treg细胞一样，TAM也可以抑制肿瘤相关抗原（TAA）特异性CD8+T细胞活化。与TAM非常相似，髓源性抑制细胞（MDSC）也可以通过CCL2–CCR2信号被招募到TEM中。此外，诱导单核细胞向肿瘤募集的其他趋化因子还有CCL5、CCL7、CCL15、CXCL8和CXCL12。浆细胞样树突状细胞（pDC）是一种罕见的免疫细胞，也能抑制抗肿瘤免疫反应。肿瘤和基质细胞产生CXCL12，它是趋化因子受体CXCR4的配体，由pDCs表达。因此，CXCL12是pDC进入TME的关键分子。此外，CXCL12还对pDC发挥保护作用，防止其发生凋亡，延长其免疫抑制作用。肿瘤生长与进展一些研究表明，趋化因子信号系统通过不同的机制参与肿瘤生长和进展。癌细胞表达的趋化因子受体与肿瘤相关成纤维细胞、肿瘤细胞和TME浸润性免疫细胞分泌的各自配体之间的相互作用可直接激活PI3K/AKT和ERK 1/2等信号通路，导致癌细胞增殖。肿瘤细胞上趋化因子受体的病理性过度表达和TME中趋化因子配体的分泌可加剧这些效应。此外，趋化因子可以通过在肿瘤细胞中产生促凋亡和抗凋亡蛋白之间的失衡，例如下调Bcl-2表达或抑制caspase-3和caspase-9激活来维持癌细胞存活，从而避免肿瘤细胞凋亡。某些免疫细胞的趋化因子募集也有助于肿瘤的发生。分泌IL-22的T辅助细胞（TH22）是TME中常见的免疫细胞亚群，已被证明通过多种途径支持肿瘤发生，特别是在结肠癌中。它们表达趋化因子受体CCR6，并向TME中存在的配体CCL20迁移，在那里它们能够通过细胞因子表达增加肿瘤细胞的干性和致瘤潜能。血管生成趋化因子及其各自的受体被认为是肿瘤血管系统的关键调节因子，在肿瘤血管生成中具有双重作用。根据N端是否存在ELR（Glu-Leu-Arg）基序，CXC趋化因子可分为两类：ELR+趋化因子和ELR−趋化因子。通过激活CXCR1和CXCR2发挥作用的ELR+CXC趋化因子，包括CXCL1、CXCL2、CXCL3、CXCL5、CXCL6、CXCL7和CXCL8，具有血管生成作用。相反，ELR−CXC趋化因子，如CXCL4、CXCL9、CXCL10、CXCL11和CXCL14被认为是血管生成抑制剂。趋化因子可以通过直接与内皮细胞上的趋化因子受体相互作用作为肿瘤血管生成介质，从而改善迁移和增殖以及内皮细胞存活。此外，趋化因子还可能通过促进TME中产生血管生成因子的白细胞的募集间接发挥作用，从而增强血管生成。趋化因子还可以与其他血管生成促进剂协同作用，如血管内皮生长因子（VEGF）。另一方面，趋化因子还具有抑制肿瘤血管生成和内皮细胞增殖的活性。例如，CXCL4和CXCL10是具有血管抑制特性的趋化因子，包括抑制由成纤维细胞生长因子和VEGF诱导的血管生成以及阻止内皮细胞趋化性和增殖。此外，CXCL9、CXCL10和CXCL11与表达CXCR3的免疫细胞的相互作用可能招募具有血管抑制功能的细胞。促进转移大量研究证实了趋化因子系统在肿瘤转移中的关键作用。据报道，癌细胞上的趋化因子受体表达可以确定其转移的部位。这些转移部位产生的特异性趋化因子可以促进循环癌细胞迁移到“转移前生态位”，这为转移细胞的生长提供了有利的环境。多种趋化因子和趋化因子受体与转移有关，CXCL12/CXCR4轴代表了这一现象的关键因素，在不同的肿瘤中已证实其参与肿瘤转移。参与癌症转移的其他趋化因子的例子有CCR7，它通过与转移部位分泌的CCL19和CCL21配体相互作用，介导癌细胞向淋巴器官的迁移；CCL28是CCR3/CCR10的配体，与乳腺癌生长和转移扩散相关；CCR10/CCL27信号支持转移扩散期间黑色素瘤细胞的粘附和存活，CXCR5/CXCL13相互作用似乎支持前列腺癌的骨转移。 -03- 二、趋化因子的靶向治疗目前，临床已批准的靶向趋化因子的药物包括：抗CCR4抗体（Mogamulizumab）和CXCR4拮抗剂（Plerixafor，AMD3100），用于血液恶性肿瘤。此外，还有更多的针对不同趋化因子受体-配体轴作为癌症治疗策略的多种努力，这些治疗策略目前已表现出巨大的潜力，正处于临床开发中。 CCR1 CCR1在几种类型的癌症中过表达，并与免疫抑制细胞浸润和转移增加有关。以CCR1为靶点的大多数治疗益处来源于减少MDSC浸润，最终抑制肿瘤生长和转移。选择性CCR1拮抗剂CCX721能够通过阻断破骨细胞减少多发性骨髓瘤（MM）骨病小鼠模型中的肿瘤负担和溶骨性病变。另一项研究报告称，使用受体拮抗剂BL5923抑制CCR1可抑制未成熟髓样细胞的募集，减少转移性结肠癌，显著延长结肠癌肝转移小鼠的生存期。CCR1拮抗剂CCX9588与抗PD-L1抗体的组合已被证明是一种很有前途的治疗方法，因为它通过抑制原位乳腺癌小鼠模型中的原发肿瘤生长和肺转移产生协同抗肿瘤作用。最近，在卵巢癌的小鼠模型中，小分子CCR1抑制剂UCB35625也能够减少细胞向大网膜的迁移，而大网膜是此类癌症的优先转移部位。总的来说，这些结果表明，以CCR1为靶点是一种可行的治疗策略，可以限制转移并延缓疾病进展。 CCR2，CCL2 已证明CCL2/CCR2轴能够将免疫抑制细胞（如MDSC和促进转移的单核细胞）招募到TME中，阻断CCL2/CCR2轴已在几种恶性肿瘤中显示出抗肿瘤作用。一些研究集中于CCR2抑制剂对胰腺癌的治疗，使用口服CCR2抑制剂PF-04136309，通过在体内小鼠模型中抑制CCR2信号来靶向TAM，可提高化疗疗效、阻断转移和增加抗肿瘤T细胞反应。在转移性胰腺导管腺癌的Ib/II期试验（NCT02732938）中，该分子与Abraxane（nab紫杉醇）和吉西他滨联合使用获得了良好的结果。另一项II期临床试验评估了CCR2抑制剂与常规化疗方案FOLFIRINOX（FX）联合应用于边缘可切除或局部晚期胰腺导管腺癌患者，证实了该疗法的安全性和耐受性。值得注意的是，使用小分子CCX872抑制CCR2提高了在胰腺癌小鼠模型中抗PD-1/ PD-L1免疫疗法的治疗效果。另一项评估CCR2拮抗剂RDC018对肝细胞癌的临床前研究显示，其抑制了肿瘤生长和转移，减少了术后复发，延长了生存期。 CCL2是受体CCR2的主要配体，阻断CCL2通过增强放疗的效果和预防转移在临床前研究中显示出抗肿瘤活性。然而，抗CCL2的单抗carlumab（CNTO 888）在实体瘤（NCT00992186）和转移性前列腺癌（NCT00537368）的1期和2期临床试验中，由于其无法降低CCL2血清水平，未能证明临床益处。 CCR4 CCR4除了是调节性T细胞的主要趋化因子受体，还在几种T细胞恶性肿瘤中过表达。抗CCR4抗体Mogamulizumab最初用于治疗难治性霍奇金淋巴瘤，目前在日本用于治疗复发性成人T细胞白血病，并在皮肤T细胞淋巴瘤的III期临床试验中成功提高了无进展生存率和生活质量。 Mogamulizumab是一种人源化单克隆抗体，具有一个去岩藻糖基化的Fc区域，以增强效应细胞结合，能够通过抗体依赖性细胞毒性（ADCC）诱导恶性T细胞消除。两项独立临床试验表明，Mogamulizumab可单独或与抗PD-1抗体Nivolumab联合安全用于晚期或转移性实体瘤的治疗。目前，还有一些其他的CCR4疗法正在开发中，包括抗CCR4 CAR-T细胞，已证明其对几种T细胞恶性肿瘤有效，以及小分子CCR4拮抗剂，能够通过防止Treg诱导提高抗癌疫苗的效力。 CCR5 抗CCR5的人源化单克隆抗体leronlimab和小分子CCR5抑制剂maraviroc和vicriviroc在几种恶性肿瘤中均显示出有希望的结果。这三种药物均能阻断免疫缺陷小鼠体内人乳腺癌异种移植物的转移，并能增强DNA损伤化疗药物对细胞的杀伤作用。Maraviroc和vicriviroc还能够在前列腺癌小鼠模型中减少全身、骨骼和大脑中的细胞转移，而Maraviroc在结直肠癌模型中限制癌相关成纤维细胞的聚集，导致肿瘤生长减少。此外，maraviroc在一项临床试验（MARACON）中显示了有希望的结果，该试验降低了对标准化疗无效的结直肠癌患者的肿瘤细胞生长，而另外两项临床试验分别评估了Pembrolizumab与maraviroc或Vicriviroc对难治性微卫星稳定结直肠癌的联合抑制作用，结果显示，延长了疾病稳定时间，生存率高于预期。目前正在对CCR5+转移性癌症患者进行其他临床试验，以评估CCR5拮抗剂与其它药物的组合。 CCR7 CCR7中和疗法在许多临床前模型中显示了有希望的结果。在前列腺癌、乳腺癌和结直肠癌模型中，通过siRNA或miRNA沉默CCR7基因表达导致转移和肿瘤生长减少。抗CCR7单克隆抗体在T细胞淋巴细胞白血病异种移植小鼠模型中显示出诱导肿瘤细胞死亡，并减少或避免中枢神经系统疾病的能力，而单链抗CCR7抗体在体外模型中成功阻止T细胞急性淋巴细胞白血病细胞通过血脑屏障。 CXCR2 CXCR2–CXCLs轴是一个重要的趋化因子，CXCR2–CXCLs轴促进肿瘤进展的机制很多，但最显著的是与中性粒细胞募集到TME和促进血管生成有关。 CXCR2的中和在各种临床前癌症模型中显示出了有希望的结果，通常作为联合治疗的一部分来规避化疗耐药性。在黑色素瘤模型中，CXCR2抑制剂Navarixin与MAPK抑制具有协同作用，而抑制剂SB225002改善了卵巢肿瘤模型中索拉非尼的抗血管生成治疗。CXCR1和CXCR2抑制剂Reparixin与5-氟尿嘧啶联合使用时，也能够改善胃癌模型中的肿瘤细胞凋亡并减少肿瘤体积。AZ13381758是一种CXCR2的小分子抑制剂，与吉西他滨联合使用时，能够减少胰腺导管腺癌模型的转移并显著延长寿命。目前，七种CXCR2抑制剂正在多项临床试验中进行研究，其中四种用于治疗转移性恶性肿瘤。其中包括用于治疗前列腺癌（2期）、头颈部鳞状细胞癌（1b/2期）和胰腺导管癌（1b/2期）的AZD5069/AZD9150；Reparixin用于治疗乳腺癌（2期）；Navarixin用于治疗前列腺癌和非小细胞癌（2期）；SX-682用于治疗III期和IV期黑色素瘤（1期）。 CXCR4 鉴于CXCR4与多种恶性肿瘤的生长和扩散具有无可争议的临床相关性，在过去十年中，已经开发出许多CXCR4靶向的肽和非肽拮抗剂。 CXCR4拮抗剂，如AMD3100和AMD3465，通过介导来自骨髓环境的肿瘤细胞的转运，增强了传统疗法的临床疗效。复发性AML患者的I/II期研究（NCT00512252）提供的数据显示，CXCR4/CXCL12轴阻断的体内疗效与令人鼓舞的缓解率之间的相关性。人源化CXCR4抗体PF-06747143在包括NHL、AML和MM在内的多种血液肿瘤模型中显示出强烈的抗肿瘤作用。在急性髓系淋巴瘤患者中进行了一项I期试验（NCT02954653），评估其安全性和耐受性，但由于主办方的原因，该试验不幸终止。最近，另一种抗CXCR4抗体ulocuplumab（BMS-936564）的Ib/II期试验（NCT01359657）证实，阻断CXCR4–CXCL12轴是安全的，并且与来那度胺和地塞米松联合治疗复发性/难治性骨髓瘤患者具有较高的应答率。 CXCR4抑制剂在实体瘤中也被证明具有重要的抗癌潜力。目前有几项临床试验正在评估CXCR4拮抗剂对胶质母细胞瘤患者的临床益处。一项I/II期试验（NCT01977677）研究了plerixafor在替莫唑胺和放射治疗后的副作用和最佳剂量，结果显示，plerixafor未观察到剂量限制性毒性，并且似乎在RT后抑制CXCL4介导的血管生成，增强了放射治疗的效果。除脑肿瘤外，AMD3465还能够预防体内乳腺癌生长和转移，而新型环肽CXCR4拮抗剂LY2510924在各种实体瘤和转移性乳腺癌临床前模型中显示出抗肿瘤活性。LY2510924在一期试验（NCT02737072）中进行试验，耐受性良好。对于HER2阴性转移性乳腺癌患者，CXCR4拮抗剂balixafortide作为单一疗法以及与其他药物联合使用的I期试验（NCT01837095）取得了有希望的初步结果。值得注意的是，CXCR4抑制也被证明能促进强烈的抗肿瘤T细胞反应。卵巢癌临床前模型中的CXCR4阻断能显著增加T细胞介导的抗肿瘤免疫反应，使AMD3100治疗的小鼠具有显著的生存优势。BPRCX807是一种选择性和有效的CXCR4拮抗剂，最近在肝细胞癌小鼠模型的体外和体内试验中显示了良好的效果。 -04- 结语趋化因子是一大类协调免疫细胞运输的趋向性的细胞因子。鉴于趋化因子在肿瘤免疫反应和肿瘤生物学中发挥着的多方面作用，趋化因子网络已成为潜在的免疫治疗靶点。趋化因子受体及其配体之间存在非常复杂的相互作用，为了引入新一代基于趋化因子调节的免疫肿瘤治疗策略，迫切需要深入了解肿瘤微环境生物学以及更好的预测性临床模型。尽管面临挑战，大量针对不同趋化因子信号通路的趋化因子受体抑制剂目前正在临床前研究和临床试验中进行评估，并且与常规化疗或免疫检查点疗法结合使用时，显示出有希望的结果。因此，可以预测，在不久的将来，趋化因子受体抑制剂将用于调节TME的组成并优化患者的免疫反应，为肿瘤患者带来希望。参考资料： 1.Chemokine-Directed Tumor MicroenvironmentModulation in Cancer Immunotherapy. Int J Mol Sci. 2021 Sep; 22(18): 9804. 公众号内回复“ADC”或扫描下方图片中的二维码免费下载《抗体偶联药物：从基础到临床》的PDF格式电子书！公众号已建立“小药说药专业交流群”微信行业交流群以及读者交流群，扫描下方小编二维码加入，入行业群请主动告知姓名、工作单位和职务。

免疫疗法

2025-03-27

·PRNewswire

LifeTracDx® Blood Test to be Performed in Key Colorectal Clinical Trial

MONMOUTH JUNCTION, N.J., March 27, 2025 /PRNewswire/ -- Creatv Bio, a Division of Creatv MicroTech, Inc. (Creatv) will be collaborating with CytoDyn Therapeutics Corporation (CytoDyn) to assess patient response to their drug using the LifeTracDx® blood test. CytoDyn has received FDA clearance to initiate a Phase II study of leronlimab in patients with relapsed or refractory micro-satellite stable colorectal cancer (CRC) (NCT06699835). The drug, leronlimab, targets CCR5 marker on the tumor. Creatv will perform the LifeTracDx® liquid biopsy in a number of CytoDyn studies including NCT06699835. The LifeTracDx® test is based on analyzing two biomarkers: (1) circulating tumor cells (CTCs) and (2) Cancer Associated Macrophage-Like (CAML) cells, which are macrophages that engulf tumor cells. Both CTCs and CAMLs contain tumor material. By tracking CTC and CAML counts, and CAML size at various time points, LifeTracDx® can provide prognostic insights and predict treatment response. CytoDyn is also interested in the expressions of CCR5 and PD-L1 markers on the tumor. These markers can change over time. LifeTracDx® can provide this information by a blood test - no tissue is required. The LifeTracDx® assay will help CytoDyn to better evaluate the effectiveness of their drug. About Creatv Bio Creatv Bio is a cancer screening and cancer diagnostics company providing testing services to patients and pharma companies to support drug development from its laboratory in NJ. Creatv's scientists were the first to publish on CAMLs found in the blood of cancer patients. LifeTracDx® blood tests have many applications including predicting response to a new therapy in just 30 days, providing companion diagnostics such as PD-L1 and drug targets using blood instead of tissue, providing information about aggressiveness of the cancer, detection of minimal residual disease, early detection of cancer recurrence, and cancer screening. For a complete listing of our journal publications and posters, please visit our website at . For more information contact: SOURCE Creatv MicroTech, Inc. WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

临床2期

100 项与 Leronlimab 相关的药物交易

登录后查看更多信息

外链

KEGG	Wiki	ATC	Drug Bank
D11399	Leronlimab	-	DB05941

研发状态

10 条进展最快的记录,

后查看更多信息

适应症	最高研发状态	国家/地区	公司	日期
HIV感染	申请上市	美国	CytoDyn, Inc.	2021-11-01
新型冠状病毒感染	临床3期	美国	CytoDyn, Inc.	2020-08-05
不能切除的大肠癌	临床2期	美国	CytoDyn, Inc.	2025-05-30
转移性结直肠癌	临床2期	-	CytoDyn, Inc.	2022-09-20
转移性微卫星稳定结直肠癌	临床2期	-	CytoDyn, Inc.	2022-09-20
微卫星稳定型结直肠癌	临床2期	-	CytoDyn, Inc.	2022-09-20
新冠肺炎后遗症	临床2期	美国	CytoDyn, Inc.	2021-03-01
非酒精性脂肪性肝炎	临床2期	美国	CytoDyn, Inc.	2020-12-01
三阴性乳腺癌	临床2期	美国	CytoDyn, Inc.	2019-04-22
急性移植物抗宿主病	临床2期	美国	CytoDyn, Inc.	2017-05-14

登录后查看更多信息

临床结果

适应症

分期

评价

查看全部结果

研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT04678830 (CTgov)	临床2期	新冠肺炎后遗症	56	Leronlimab (700mg) (700mg Leronlimab)	醖餘鑰膚淵觸夢糧淵蓋(觸構願鬱艱憲製製構襯) = 襯鬱醖憲顧膚選鑰鹹繭蓋憲蓋窪鹹夢蓋廠窪艱 (膚醖夢淵鬱遞鹹蓋夢壓, 13.14) 更多	-	2024-04-11
				Placebos (Placebo)	醖餘鑰膚淵觸夢糧淵蓋(觸構願鬱艱憲製製構襯) = 積襯襯積窪鹽繭範糧糧蓋憲蓋窪鹹夢蓋廠窪艱 (膚醖夢淵鬱遞鹹蓋夢壓, 12.27) 更多
NCT02737306 (GVHD, CTgov)	临床2期	急性髓性白血病 \| 急性移植物抗宿主病 \| 骨髓增生异常综合征	11	Placebo	襯衊餘齋夢糧艱鏇糧窪(願衊糧餘憲廠構衊鑰膚) = 醖遞鏇繭選願艱窪鹽獵窪鹽鹹襯鏇蓋繭壓蓋積 (鏇壓鹽夢鹽鏇範繭齋衊, 憲積遞獵鹽觸獵糧構遞 ~ 衊齋範觸網築顧窪顧襯) 更多	-	2024-03-12
NCT02175680 (CTgov)	临床2期	HIV感染	43	Historical data+PRO 140	糧醖選壓鏇壓餘鹹衊顧(餘遞糧壓憲積製憲糧壓) = 鑰艱選膚襯簾鏇製夢窪艱築鏇願淵窪積鹽鹽齋 (鹹願獵夢艱淵範願蓋積, 0.71) 更多	-	2023-04-14
NCT00110591 (CTgov)	临床1期	HIV感染	20	PRO 140 (Placebo)	鬱顧膚繭構夢壓憲顧鏇 = 觸簾夢鹽淵壓齋繭窪顧齋淵積鑰窪願遞鑰鏇築 (積構願網夢鏇鹽製廠夢, 築願觸襯製顧遞構膚範 ~ 襯築醖壓夢築願願襯齋) 更多	-	2023-03-14
				PRO 140 (PRO 140 Dose 1)	鬱顧膚繭構夢壓憲顧鏇 = 淵鏇艱壓艱衊遞選製積齋淵積鑰窪願遞鑰鏇築 (積構願網夢鏇鹽製廠夢, 選淵鏇鏇範糧壓窪顧夢 ~ 膚齋衊簾餘範積膚糧範) 更多
NCT04521114 (NASH, CTgov)	临床2期	非酒精性脂肪性肝炎	87	leronlimab 700 mg (Leronlimab 700 mg)	襯鑰願膚鹹醖範範窪淵(廠壓繭膚衊觸觸顧窪窪) = 廠襯憲鑰窪襯範鹽觸醖遞觸製顧範膚築蓋齋遞 (願繭蓋鏇獵願鏇鹹觸構, 積構鏇壓製蓋憲選範鹹 ~ 網廠鏇製遞糧鏇衊鬱鬱) 更多	-	2023-03-01
				leronlimab 350 mg (Leronlimab 350 mg)	襯鑰願膚鹹醖範範窪淵(廠壓繭膚衊觸觸顧窪窪) = 積範網簾繭構衊淵簾壓遞觸製顧範膚築蓋齋遞 (願繭蓋鏇獵願鏇鹹觸構, 膚簾憲願膚鏇鏇選選淵 ~ 鏇艱艱遞構蓋選鹹選鬱) 更多
NCT04343651 (CTgov)	临床2期	新型冠状病毒感染	86	Placebo (Placebo)	願繭鹹鏇糧艱廠壓蓋簾(簾築構顧艱齋壓齋鹹簾) = 醖築繭糧簾鹽網糧繭積選蓋蓋願鑰窪願鏇淵艱 (憲獵艱鬱憲築夢觸構齋, 3.19) 更多	-	2023-01-04
				Leronlimab (700mg) (700mg Leronlimab)	願繭鹹鏇糧艱廠壓蓋簾(簾築構顧艱齋壓齋鹹簾) = 廠網遞醖獵範觸鹹築鏇選蓋蓋願鑰窪願鏇淵艱 (憲獵艱鬱憲築夢觸構齋, 3.03) 更多
NCT02483078 (PRO140, CTgov)	临床2/3期	HIV感染	52	Optimized Background Regimen+PRO 140 (PRO 140)	廠觸糧觸艱膚窪餘膚襯 = 簾蓋範醖製積襯齋繭壓觸醖選積觸獵簾網簾夢 (積夢壓選觸繭蓋夢醖齋, 淵衊鑰積簾積製選構築 ~ 鏇艱鹽膚構襯簾蓋遞構) 更多	-	2022-11-03
				Placebo (Placebo)	廠觸糧觸艱膚窪餘膚襯 = 願願齋襯願築範觸簾齋觸醖選積觸獵簾網簾夢 (積夢壓選觸繭蓋夢醖齋, 餘觸獵獵膚鑰艱膚積鑰 ~ 簾夢繭衊餘鏇廠鑰膚膚) 更多
NCT03838367 \| NCT04504942 \| NCT04313075 (ASCO2022) 人工标引	临床1/2期	三阴性乳腺癌	68	Leronlimab	憲願憲選壓糧構醖築觸(構淵簾鏇襯範願廠積鑰) = 繭製選餘築鹽鏇蓋觸齋膚醖襯範餘襯夢廠構艱 (窪願製淵鏇夢夢獵積獵, 2.3 ~ 6.2) 更多	积极	2022-06-02
SABCS2022	N/A	三阴性乳腺癌	-	Leronlimab	選構夢願襯醖艱夢願遞(廠鬱餘糧構繭衊簾選蓋) = n=2 簾構糧憲鹽積獵鑰簾構 (醖範憲淵憲窪廠窪選願 ) 更多	-	2022-02-15
NCT03838367 (GlobeNewswire) 人工标引	临床1/2期	三阴性乳腺癌 triple-negative	30	Carboplatin+leronlimab	築蓋糧製遞憲繭觸製顧(蓋構糧簾遞選壓醖蓋簾) = 壓遞選願膚鏇築蓋膚繭夢艱遞蓋獵廠壓選選鹽 (衊衊鏇願簾壓壓繭壓廠 ) 更多	积极	2021-07-19