MC1963 Folate Receptor Alpha Dendritic Cells (FRαDCs) or Placebo for Patients With Advanced Stage Ovarian Cancer: A Phase II Double-Blind Randomized Clinical Trial (FAROUT)

This phase II trial compares the effect of folate receptor alpha dendritic cells (FRαDCs) to placebo in treating patients with stage III or IV ovarian, fallopian tube or primary peritoneal cancer. FRαDCs, a dendritic cell vaccine, is made from a person's white blood cells. The white blood cells are treated in the laboratory to make dendritic cells (a type of immune cell) mixed with folate receptor alpha (FRalpha), a protein found in high levels on ovarian tumor cells. FRαDCs work by boosting the immune system to recognize and destroy the tumor cells by targeting the FRalpha protein on the tumor cell. Placebo is an inactive substance that looks the same as, and is given the same way as, the active drug or treatment being tested. The effects of the active drug are compared to the effects of the placebo. Giving FRαDCs may work better in preventing or delaying recurrence compared to placebo in patients with stage III or IV ovarian, fallopian tube, or primary peritoneal cancer.

开始日期2024-11-08

申办/合作机构

Mayo Clinic

NCT02978222

/ Terminated临床2期

A Randomized Multicenter Phase II Trial to Evaluate the Safety, Efficacy and Immunogenicity of Vaccination With Folate Receptor Alpha Peptides With GM-CSF Versus GM-CSF Alone in Patients With Platinum Sensitive Ovarian Cancer and a Response or Stable Disease to Platinum Therapy

This is a double-blind, randomized, parallel groups Phase II trial. Patients with platinum-sensitive advanced ovarian cancer, defined as a lack of progression by RECIST v1.1 criteria following completion of standard-of-care chemotherapy, including a minimum of 4 cycles of a platinum-containing regimen. Patients will be randomized to either the vaccine regimen with GM-CSF adjuvant or GM-CSF adjuvant alone as a control group. Treatment will be administered as a consolidation therapy within one year of the last administration of platinum, targeting the first remission.

开始日期2017-07-20

申办/合作机构

Marker Therapeutics, Inc.

NCT02764333

/ Completed临床2期IIT

A Phase II Trial of TPIV200/huFR-1 (A Multi-Epitope Anti-Folate Receptor Vaccine) Plus Anti-PD-L1 MEDI4736 (Durvalumab) in Patients With Platinum Resistant Ovarian Cancer

This is a Phase 2 clinical trial, which tests two investigational drugs: TPIV200/huFR-1 (also called TPIV200), which is a vaccine consisting of proteins from the folate receptor alpha mixed with GM-CSF, and durvalumab (MEDI4736) , which is an antibody drug that help un-block parts of the immune system. The aim of this study is to find out whether these drugs, when given together are safe, and whether they are effective in treating cancer.

开始日期2016-05-06

申办/合作机构

Memorial Sloan Kettering Cancer Center

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100 项与 Folate receptor alpha vaccine(Mayo Clinic) 相关的临床结果

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100 项与 Folate receptor alpha vaccine(Mayo Clinic) 相关的转化医学

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100 项与 Folate receptor alpha vaccine(Mayo Clinic) 相关的专利（医药）

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项与 Folate receptor alpha vaccine(Mayo Clinic) 相关的文献（医药）

2024-10-01·GYNECOLOGIC ONCOLOGY

Vaccination with folate receptor-alpha peptides in patients with ovarian cancer following response to platinum-based therapy: A randomized, multicenter clinical trial

Article

作者: Potts, James ; Knutson, Keith L ; Kenney, Richard T ; Wenham, Robert M ; O'Cearbhaill, Roisin E ; Block, Matthew S ; Garrett, Gerald ; Hamilton, Erika ; Gupta, Aditi ; Konner, Jason A

OBJECTIVE:

Folate receptor alpha (FRα) is overexpressed on >90% of high-grade epithelial ovarian cancers (EOC). Targeting FRα with antibody-drug conjugates has proven utility in the platinum-resistant setting. It is also a potential therapeutic target for immuno-oncologic agents, such as peptide vaccines that work primarily via adaptive and humoral immunity. We tested the hypothesis that FRα peptide immunization could improve outcomes in patients with EOC following response to platinum-based therapy.

METHODS:

We conducted a randomized, double-blind, multicenter, phase II study to evaluate the safety and efficacy of TPIV200 (a multi-epitope FRα peptide vaccine admixed with GM-CSF) versus GM-CSF alone in 120 women who did not have disease progression after at least 4 cycles of first-line platinum-based therapy. Patients were vaccinated intradermally once every 4 weeks up to 6 times, followed by a boosting period of 6 vaccinations at 12-week intervals. Primary endpoints included safety, tolerability, and progression free survival (PFS).

RESULTS:

At study termination with a median follow-up of 15.2 months (range 1.2-28.4 months), 68 of 119 intention-to-treat patients had disease progression (55% in TPIV200 + GM-CSF arm and 59% in GM-CSF alone arm). The median PFS was 11.1 months (95% CI 8.3-16.6 months) with no significant difference between the treatment groups (10.9 months with TPIV200 + GM-CSF versus 11.1 months with GM-CSF, HR, 0.85; upper 90% CI 1.17]. No patient experienced a ≥ grade 3 drug-related adverse event.

CONCLUSION:

TPIV200 was well tolerated but was not associated with improved PFS. Additional studies are required to uncover potential synergies using multiepitope vaccines targeting FRα. Trial Registration NLM/NCBI Registry, NCT02978222, https://clinicaltrials.gov/search?term=NCT02978222.

2020-06-01·Journal for immunotherapy of cancer2区 · 医学

Safety, immunogenicity, and clinical efficacy of durvalumab in combination with folate receptor alpha vaccine TPIV200 in patients with advanced ovarian cancer: a phase II trial

2区 · 医学

ArticleOA

作者: Torrisi, Jean M ; Zamarin, Dmitriy ; Holland, Aliya ; Erskine, Courtney L ; O’Cearbhaill, Roisin E ; Aghajanian, Carol ; Li, Yanyun ; Mcdonnell, Autumn S ; Konner, Jason A ; Knutson, Keith L ; Hollmann, Travis J ; Grisham, Rachel N ; Chesebrough, Lewis F ; Gallagher, Jacqueline M ; Block, Mathew S ; Walderich, Sven ; Merghoub, Taha ; Iasonos, Alexia E ; Zhou, Qin

Background:

Immune checkpoint inhibitors (ICIs) to date have demonstrated limited activity in advanced ovarian cancer (OC). Folate receptor alpha (FRα) is overexpressed in the majority of OCs and presents an attractive target for a combination immunotherapy to potentially overcome resistance to ICI in OCs. The current study sought to examine clinical and immunologic responses to TPIV200, a multiepitope FRα vaccine administered with programmed death ligand 1 (PD-L1) inhibitor durvalumab in patients with advanced platinum-resistant OC.

Methods:

Following Simon two-stage phase II trial design, 27 patients were enrolled. Treatment was administered in 28-day cycles (intradermal TPIV200 and granulocyte-macrophage colony-stimulating factor (GM-CSF) for 6 cycles and intravenous durvalumab for 12 cycles). Primary endpoints included overall response rate and progression-free survival at 24 weeks. Translational parameters focused on tumor microenvironment, PD-L1 and FRα expression, and peripheral vaccine-specific immune responses.

Results:

Treatment was well tolerated, with related grade 3 toxicity rate of 18.5%. Increased T cell responses to the majority of peptides were observed in all patients at 6 weeks (p<0.0001). There was one unconfirmed partial response (3.7%) and nine patients had stable disease (33.3%). Clinical benefit was not associated with baseline FRα or PD-L1 expression. One patient with prolonged clinical benefit demonstrated loss of FRα expression and upregulation of PD-L1 in a progressing lesion. Despite the low overall response rate, the median overall survival was 21 months (13.5–∞), with evidence of benefit from postimmunotherapy regimens.

Conclusions:

Combination of TPIV200 and durvalumab was safe and elicited robust FRα-specific T cell responses in all patients. Unexpectedly durable survival in this heavily pretreated population highlights the need to investigate the impact of FRα vaccination on the OC biology post-treatment.

CLINICAL CANCER RESEARCH

A phase II trial to evaluate the safety and immunogenicity of two doses of a folate receptor alpha vaccine in patients with triple negative breast cancer

Article

作者: Graff, Stephanie L. ; Sparano, Joseph A. ; Cogen, Davitte ; Erskine, Courtney L. ; Hamilton, Erika P. ; Norton, Nadine ; Block, Matthew S. ; Tiersten, Amy ; Assad, Hadeel ; Knutson, Keith L. ; Wilson, Glynn ; McIntyre, Kristi J. ; Abu-Fares, Hala ; Han, Hyo S. ; Nassar, Aziza ; Garrett, Gerald ; Tkaczuk, Katherine H. ; Kenney, Richard T. ; Keating, Patricia ; Sharma, Priyanka ; Ward, Patrick J.

Abstract:

Purpose: CD4 T cell immunity is associated with improved survival in patients with breast cancer. We previously reported a Phase I trial evaluating a folate receptor alpha (FRα) vaccine administered with cyclophosphamide (CP), demonstrating excellent safety and immunogenicity. To simplify the vaccine strategy for ease of use, we report here the results of a randomized Phase II trial evaluating a lower vaccine dose alongside the original dose, administered with or without cyclophosphamide pretreatment. Patients and Methods: Patients with triple-negative breast cancer (TNBC) who completed all systemic and local therapy were assigned to receive either Low-dose (825 mg) or High-dose (2.5 mg) vaccine peptides plus GM-CSF in six 4-week cycles, with or without CP prior to vaccination. Safety was monitored and immunogenicity was evaluated pre- and post-vaccination. Results: A total of 80 patients were dosed with vaccine, and 58 patients were evaluable for immunogenicity. Vaccination was well tolerated and elicited immunity in 83% of patients. Levels of FRα-specific T cells were high, persistent, and comparable to T cell levels against tetanus toxoid. No differences in immunity were observed between the two doses. CP pretreatment also did not affect the immune responses. Recurrences occurred in 8 evaluable patients and were unrelated to the treatment arm. No patients died during the study due to their disease. Conclusions: The reduced dose FRα vaccine is as effective as the original dose and does not require CP to generate maximal immunity. These findings may inform the design of trials testing efficacy in TNBC or other cancers.

项与 Folate receptor alpha vaccine(Mayo Clinic) 相关的新闻（医药）

2025-10-31

·FiercePharma

Pediatrician group declines to back leucovorin for routine use against autism

The American Academy of Pediatrics acknowledged that small studies have pointed to “potential benefit in carefully selected cases,” but said large clinical trials are needed to determine leucovorin’s efficacy and safety profile for the broader autism population. The American Academy of Pediatrics (AAP) on Friday said it does not recommend the routine use of leucovorin for children with autism.Calls for the professional association of pediatricians to provide guidance on leucovorin for autism emerged in September after U.S. health officials positioned the decades-old drug as a treatment for cerebral folate deficiency (CFD), which is present in some children with autism spectrum disorder (ASD).As the FDA works with GSK to allow the British pharma’s previously discontinued leucovorin product Wellcovorin to treat CFD, the Department of Health and Human Services said in a Sept. 22 release that the move will “authorize treatment for children with ASD,” and that state Medicaid programs will be able to cover the drug for the indication of autism. But in an “interim guidance” posted Friday, the AAP said “the current evidence base remains too limited to support” recommendations for the drug, suggesting that large clinical trials are needed to determine leucovorin’s efficacy and safety profile for the broader autism population. In its Sept. 22 release, the HHS said the National Institutes of Health will launch confirmatory trials and new research into the effects of leucovorin.“The AAP does not have prescribing guidelines for leucovorin for the indication of autism,” the organization said.In some children with autism, folate receptor alpha (FRα) autoantibodies block the transport of folate—a B vitamin—into the brain, leading to CFD. Leucovorin, or folinic acid, bypasses the defective folate transport system and delivers folate directly to the brain, according to an HHS fact sheet. To back its decision on Wellcovorin, the FDA cited a “systematic analysis of literature published between 2009-2024, including published case reports with patient-level information, as well as mechanistic data.”In a double-blind, placebo-controlled trial among 80 patients, researchers in India recorded better changes in Childhood Autism Rating Scale scores, as well as better changes in behavioral problems measured by the Child Behavior Checklist, for those who took leucovorin versus placebo. In the leucovorin group, improvement was more pronounced in children with higher levels of folate receptor autoantibodies.The study was clearly too small, based on a recent Centers for Disease Control and Prevention estimate that in 2022, 1 in 31 children were diagnosed with autism by age 8 in the U.S.The APP acknowledged that small studies have pointed to “potential benefit in carefully selected cases,” and that these “preliminary results are promising and have laid the groundwork for further investigation.”The organization also said guidance needs “to be grounded in both scientific rigor and respect for neurodiversity.”The doctors’ association previously blasted the Trump administration for linking autism to childhood vaccines and to the use of the pain reliever acetaminophen during pregnancy without evidence. It also criticized the administration for aggressively promoting leucovorin as an autism treatment.Following a Sept. 22 White House press conference on autism, AAP President Susan Kressly, M.D., said in a statement that the event was “filled with dangerous claims and misleading information that sends a confusing message to parents and expecting parents and does a disservice to autistic individuals.”“Don’t take Tylenol,” President Donald Trump repeatedly said during the Sept. 22 press conference, referring to the original Kenvue drug by its brand name. But during an Oct. 29 event, U.S. Health Secretary Robert R. Kennedy Jr. said there’s no sufficient evidence to definitely link Tylenol to autism.“The causative association… between Tylenol given in pregnancy and the perinatal periods is not sufficient to say it definitely causes autism. But it is very suggestive,” Kennedy said, as cited by Reuters.“There should be a cautious approach to it,” he added.Kenvue has pushed back against the claim by the Trump administration, having urged the FDA not to change the label of the popular pain medication over the uncorroborated link between its pregnancy use and autism.Meanwhile, Texas Attorney General Ken Paxton has filed a new lawsuit against the Johnson & Johnson consumer health spinoff, alleging the company “deceptively” marketed Tylenol to pregnant women despite knowing exposure to the drug can cause a “significantly increased risk of autism and other disorders.”

2025-05-23

·靶点圈

一文读懂：叶酸受体α（FRα）与多种癌症的神秘关联及靶向治疗突破

01叶酸及叶酸转运体概述叶酸代谢与肿瘤药物研发叶酸代谢在人体生物化学中至关重要，参与一碳代谢，有助于三个基本的生物合成途径：从头核苷合成、甲基化反应和氨基酸生产。但在肿瘤发生过程中会被破坏，可为肿瘤细胞的增殖提供物质基础，因此长期以来都是肿瘤药物研发的热门靶点。早期的抗叶酸药物如氨蝶呤及其后续的甲氨蝶呤、培美曲塞等，至今仍在临床广泛应用。叶酸与叶酸转运体叶酸即维生素B9，是人体必需的营养素，缺乏会导致贫血和发育缺陷。饮食中的叶酸无生物活性，需还原为活性四氢叶酸(THF)形式且携带不同的一碳单位，才能参与细胞的生物合成过程。叶酸是亲水性阴离子分子，难以自由穿过生物膜，其进入哺乳动物细胞依赖于还原型叶酸载体(RFC)、质子偶联叶酸转运体(PCFT)和叶酸受体(FRs)三种主要的转运体。图1 三种类型的叶酸转运蛋白叶酸受体(FRs)亚型FRs有四种亚型，分别为FRα、FRβ、FRγ和FRδ，由FOLR1-4基因编码，其中FRα是研究的重点。各亚型在叶酸结合亲和力和组织分布上存在差异。FRβ存在于胎盘、造血组织等，在肿瘤相关巨噬细胞中高表达，可作为M2调节性巨噬细胞极化的生物标志物和潜在免疫治疗靶点；FRγ是分泌蛋白，主要在造血组织表达，功能尚不明确；FRδ缺乏经典的叶酸结合口袋，对叶酸亲和力低，在受精过程中起重要作用，还可能是CD4+T滤泡辅助细胞激活的生物标志物。表1 叶酸受体亚型在正常组织和恶性组织中的分布与表达02FRα的生物学特征概述FRα的结构FRα是一种38-40kDa富含半胱氨酸的糖蛋白，通过羧基末端的GPI锚定在细胞膜上。它具有球状结构，包含一个深而开放的叶酸结合口袋，能高亲和力结合叶酸及其衍生物，这种结构特点为设计叶酸偶联药物和抗FRα疗法提供了基础。图2 FRα和叶酸之间的相互作用示意图FRα的表达在正常生理情况下，FRα主要表达在脉络丛、肺、甲状腺、视网膜和胎盘等极化上皮细胞的顶端或腔面。在病理情况下，多种肿瘤组织中FRα过表达。图3 FRα在恶性和正常组织中的表达FRα的氨基酸序列SignalChainPropeptide1-2424-234235-257MAQRMTTQLLLLLVWVAVVGEAQTRIAWARTELLNVCMNAKHHKEKPGPEDKLHEQCRPWRKNACCSTNTSQEAHKDVSYLYRFNWNHCGEMAPACKRHFIQDTCLYECSPNLGPWIQQVDQSWRKERVLNVPLCKEDCEQWWEDCRTSYTCKSNWHKGWNWTSGFNKCAVGAACQPFHFYFPTPTVLCNEIWTHSYKVSNYSRGSGRCIQMWFDPAQGNPNEEVARFYAAAMSGAGPWAAWPFLLSLALMLLWLLSFRα的生理功能FRα作为叶酸转运体，结合叶酸衍生物，参与叶酸的摄取和转运；可作为转录因子发挥作用；还在胚胎发育中至关重要，可能介导胚胎神经管的形成、母婴间的叶酸转运。缺乏FRα会导致胚胎发育异常、器官功能受损等问题。图4 FRα介导的细胞内吞作用和信号通路FRα在肿瘤中的作用①促进肿瘤细胞代谢：FRα通过为癌细胞提供叶酸，促进肿瘤细胞代谢，进而推动肿瘤发生。然而，由于叶酸稳态主要由RFC控制，FRα在这一过程中的重要性存在争议。②驱动肿瘤发展的转录因子功能：FRα的核转位与癌细胞的增殖以及癌症干细胞的重编程有关，其可激活多个转录因子，如OCT4/SOX2、KLF4、HES1和FGFR4等，这些转录因子分别调节干细胞特性、细胞重编程、转移和多药耐药以及细胞增殖。③与促癌信号通路相互作用：FRα可直接与促进肿瘤发生的信号通路相互作用。例如，叶酸-FRα复合物能借助共受体gp130，以JAK依赖的方式激活致癌的STAT3；FRα还被认为与丝氨酸/苏氨酸激酶ERK1/2相互作用，调节TP53基因转录；在卵巢癌中，敲低FRα可通过下调细胞-细胞粘附分子E-cadherin，抑制细胞增殖和迁移。图5 FRα表达与癌症发展之间的相关性03FRα在癌症诊断和治疗中的应用癌症诊断方面作为诊断标志物：FRα在多种癌症中呈现高表达，像卵巢癌、乳腺癌、子宫内膜癌等，而在正常组织中表达有限，这种差异表达使其可作为诊断癌症的重要生物标志物。例如，通过检测血清中FRα的含量，有助于卵巢癌的早期诊断和病情监测。多种检测手段的核心：多种方法可用于检测FRα活性，实现癌症的精准诊断。如全身单光子发射CT、FRα-靶向对比增强磁共振成像(MRI)等，能在分子和细胞水平可视化癌症变化，为早期检测和个性化治疗提供依据。表2 FRα表达水平升高的癌症类型的各种例子癌症治疗方面指导靶向治疗：FRα的过表达特性使其成为癌症靶向治疗的理想靶点。基于此开发的多种治疗方法，如叶酸偶联物、单克隆抗体等，可将细胞毒性药物精准输送到癌细胞，减少对健康细胞的损害。免疫治疗的重要靶点：针对FRα产生的抗体，可介导免疫细胞对肿瘤细胞的杀伤作用，为癌症免疫治疗提供了新策略。免疫介导的靶向FRα阳性肿瘤的治疗方法，包括过继转移肿瘤特异性T淋巴细胞、双特异性抗体靶向T细胞疗法和免疫细胞因子等，能有效抑制癌细胞的生长和转移。增强治疗效果：通过调节FRα的表达，可以提高抗癌治疗的效果。在卵巢癌治疗中，顺铂与FRα的相互作用影响癌细胞的凋亡和细胞周期，FRα过表达的癌细胞对顺铂更敏感，因此FRα可作为提高卵巢癌对顺铂治疗敏感性的潜在靶点。图6 FRα在癌症诊断和治疗中的潜在应用的未来方向局限性靶向FRα进行癌症诊断和治疗都存在一定局限性。诊断方面，检测方法存在灵敏度和特异性的问题，且放射性标记的叶酸主要成像于脾脏、肝脏和肾脏的FR，其他组织的FR难以检测。治疗方面，虽然副作用较少，但癌症细胞可能对治疗产生耐药性，且治疗费用较高。04FRα的靶向药物及其他应用图7 FRα靶向疗法及其作用机制单克隆抗体如Farletuzumab、KHK2805、MOv19、MOv18-IgG1和MOv18-IgE等，它们通过不同机制发挥抗癌作用，部分已进入临床试验阶段，但结果各异。Farletuzumab是一种人源化IgG1单克隆抗体，通过激活补体依赖的细胞毒性(CDC)等机制发挥抗癌作用，临床试验显示其在部分患者中有效，但在一些试验中未达到预期疗效。KHK2805是一种新型人源化抗体，对FRα不同表位有高亲和力，采用去岩藻糖基化设计，增强ADCC和CDC活性，在卵巢癌临床前模型中展现出显著活性，但后续开发情况不明。MOv19是一种通过杂交瘤技术制备的鼠源IgG2a抗体。此外，MOv19还被广泛改造用于多种治疗策略，其经改造生成了嵌合抗体ChiMOv19和人源化衍生物M9346A。MOv18-IgG1是与MOv19平行产生的抗体，鼠源MOv18克隆经放射性标记用于评估临床可行性，但患者易产生人抗鼠抗体(HAMA)。改造后的嵌合MOv18抗体可发挥ADCC活性，在早期试验中能有效定位到卵巢癌组织，但后续未再有开发报道。MOv18-IgE是首个针对FRα的嵌合IgE抗体，基于IgE的特性，在临床前模型中展现出良好疗效，但在早期临床试验中发现可能会引发短暂性荨麻疹等副作用。CAR-T细胞疗法通过工程化改造T细胞，使其表达针对FRα的抗原特异性单链可变片段抗体，从而靶向肿瘤细胞。针对FRα的CAR-T细胞疗法在临床前研究中显示出抗癌潜力，但I期试验中因T细胞存活不佳未观察到肿瘤负担减轻，目前研究主要集中在提高T细胞的持久性和疗效上。如MOv19-BBζ等第二代抗FRα-CAR-T细胞构建体，在体内试验中展现出更好的T细胞持久性和抗肿瘤活性，但该疗法面临鼠源scFv序列引发HAMA反应等问题。图8 CAR-T细胞疗法TIL疗法利用从患者肿瘤中收集的T细胞，与FRα靶向分子结合进行治疗。例如ITIL-306，可增强T细胞活性，目前一项评估其安全性和可行性的多癌种1期剂量递增和扩展研究正在进行中。表3 靶向FRα的临床开发中的抗体和T细胞疗法示例抗体-药物偶联物多种ADC药物正在研发中，Mirvetuximab-Soravtansine(MIRV)是首个获批用于治疗FRα阳性铂耐药卵巢癌的ADC药物，由人源化抗FRα单克隆抗体、可裂解连接子和细胞毒性药物DM4组成，但可能导致可逆性眼部不良事件。此外，MORAb-202、Luveltamab-Tazevibulin和STRO-002等ADC药物也在进行临床试验，各自具有独特的结构和作用机制，显示出一定的潜力。图9 FRα的ADC药物结构示意图以及MIRV的作用机制表4 靶向FRα的临床开发中的ADC示例叶酸-药物偶联物(FDCs)将细胞毒性药物与叶酸结合，通过FRα进入细胞发挥作用。Vintafolide是较为成功的FDC，但在III期临床试验中未达到预期效果，其他FDCs如EC131、EC2629等仍处于研究阶段。图10 Vintafolide的结构及其作用机制疫苗以FRα为靶点的疫苗可诱导免疫系统产生抗体，作为维持治疗手段预防疾病复发。早期研究证实了其安全性，与免疫检查点抑制剂联合使用可增强T细胞反应，目前相关试验主要在乳腺癌和卵巢癌患者中开展。表5 以FRα为靶点的疫苗的临床试验小分子-药物偶联物(SMDCs)叶酸-药物偶联物如EC145，在前期试验有一定效果，但III期临床试验未达到无进展生存期终点，且部分药物因毒性问题研发停滞。BGC945是一种针对FRα的胸苷酸合酶抑制剂，在I期临床试验中观察到对部分卵巢癌患者有临床益处。表6 FRα的临床试验清单联合治疗策略与化疗联合：多数FRα靶向单克隆抗体已与化疗联合应用，但尚无单克隆疗法在3期研究中显示出优于标准化疗的生存获益。相比之下，ADC联合化疗的研究相对较少，但部分ADC与化疗联合在临床前研究中显示出更好的抗肿瘤效果，相关临床试验正在进行中，有望确定新的治疗标准。与靶向药物和免疫疗法联合：如MIRV与贝伐单抗、免疫疗法药物的联合治疗，初步研究显示出一定的潜力，但仍需进一步临床试验验证。FRα的其他应用术中肿瘤识别：FDA批准的荧光药物Pafolacianine可与FRα结合，用于术中识别卵巢癌和肺癌的残留或隐藏肿瘤，提高手术的精准性和患者的预后。在卵巢癌手术研究中，33%的FRα阳性患者通过该方法检测出残留癌组织，检测灵敏度达83%，且62.4%的患者实现了完全R0切除，有助于提高手术精准度，改善患者预后。纳米颗粒疗法：FRα在癌细胞中高表达且能被细胞内吞，借助纳米技术可将化疗药物精准递送至癌细胞，增强治疗效果并减少全身副作用。如肝素-叶酸-紫杉醇(HFT)、Nab-紫杉醇-叶酸等纳米颗粒结合物已在多种癌症治疗中显示出优势，提高了药物递送效率和肿瘤杀伤效果，为癌症治疗提供了新策略。预后标志物：多项研究表明，FRα表达水平与多种癌症的预后相关。在乳腺癌、肺癌、子宫内膜癌和卵巢癌等多种癌症中，FRα高表达往往与患者较差的总生存期(OS)相关，且与肿瘤分级、结节数量和FIGO分期等相关。但在三阴性乳腺癌中，其表达与较好的无侵袭性疾病生存期(IDFS)相关，可辅助医生预测患者预后，制定更合适的治疗方案。化疗耐药替代指标：FRα表达与化疗耐药有关，在卵巢癌中，FRα高表达的患者对化疗反应不佳，它可抑制细胞毒性药物诱导的细胞凋亡。它可能通过调节MDM2和p53等分子影响癌细胞对化疗药物的敏感性。未来，FRα有望作为化疗耐药的替代指标，指导临床选择更有效的治疗方案。ctDNA检测：通过ApoStream技术和激光扫描cytometry可检测血液中FRα阳性的循环肿瘤细胞(CTCs)，为FRα表达癌症的诊断、监测和治疗指导提供了一种非侵入性方法，在非小细胞肺癌中，FRα-ctDNA可作为EGFR阳性的替代指标，辅助诊断。05HER3在多种癌症中的异常表达及影响卵巢癌FRα在约80%的原发性和复发性卵巢癌中过表达，其高表达与疾病分期和分级相关，血清sFR可作为EOC复发标志物，可通过下调肿瘤抑制因子cav-1促进肿瘤发生。可作为生物标志物用于疾病监测、判断患者对治疗的反应以及筛选适合靶向治疗的患者。此外，对一线铂类治疗耐药且术后有残留疾病的患者，其FRα水平较高，具有预后价值，且化疗不影响FRα表达，因此FRα拮抗剂成为上皮性卵巢癌的研究靶点，为卵巢癌治疗带来了新希望。宫颈癌和子宫内膜癌宫颈癌恶性转化时，FRα染色情况会发生变化，且其与FR活性相关，FRα及ERK信号蛋白水平与宫颈病变严重程度正相关。在子宫内膜癌中，FRα过表达与预后不良和无进展生存期缩短有关，且FRα表达水平在子宫内膜样腺癌中显著高于子宫内膜增生，可能参与恶性转化，可作为早期干预的靶点。乳腺癌在乳腺癌研究中，FRα状态与分期及其他标志物相关。其过表达与不良预后相关，包括无病生存期降低，通过PET和MRI等成像技术可检测其表达，指导治疗。在I-III期浸润性导管癌中，30%的样本呈FRα阳性，且三阴性乳腺癌(TNBC)与FRα阳性相关性最强，FRα的表达与较好的无侵袭性疾病生存期(IDFS)相关，但对总生存期(OS)的影响存在争议。雌激素受体阳性可能对高FRα水平有保护作用并下调其表达，因此高FRα表达的TNBC患者值得进一步研究并采用靶向抗叶酸疗法。肺癌在肺癌方面，约72%的恶性胸膜间皮瘤FRα水平升高2-4倍，但使用培美曲塞治疗，对FRα高表达患者的疗效改善不明显。在非小细胞肺癌(NSCLC)中，FRα表达与快速细胞周转相关，且与较好的预后有关。FRα在肺腺癌中表达更高，尤其是表皮生长因子受体(EGFR)突变的肿瘤以及非吸烟者和早期阶段的肿瘤。这使得FRα成为NSCLC治疗的一个有潜力的靶点，针对FRα的研究可能为NSCLC患者提供更精准的治疗方案。头颈部鳞状细胞癌头颈部鳞状细胞癌中，FRα阳性与不良临床结局相关，约45%的原发性肿瘤呈FRα阳性，无FRα阳性表达的患者生存期更长，提示FRα高表达是疾病严重程度和死亡率的重要风险因素。胃肠道癌症在胃肠道癌症中，FRα的存在与多种因素相关，可作为预后因素及潜在的治疗靶点。在胃癌中，FRα的表达与预后不良相关，且与淋巴血管浸润和淋巴结外疾病有关。它可作为一种非侵入性筛查工具，用于胃癌的早期诊断，比癌胚抗原(CEA)更具优势。在结直肠癌中，其表达与癌组织相关(33%-44%的癌组织表达，而正常结肠组织或腺瘤仅7%)，且与患者年龄、转移及非高频微卫星不稳定状态有关。研究发现，IV期结直肠癌伴肝转移患者中，术后生存期短的患者FRα表达显著更高。在胰腺癌中，FRα阳性的手术标本患者预后较差，不过其对无进展生存期影响不显著。此外，胰腺癌还主要表达FRβ，可作为分子靶向治疗的考虑对象。其他癌症在间皮瘤、口腔癌、黑色素瘤等癌症中，FRα也呈现高表达状态。在间皮瘤中，其表达情况影响治疗方案的选择；在口腔癌中，可利用FRα将化疗药物靶向递送至癌细胞，增强治疗效果；在黑色素瘤中，纳米颗粒技术借助FRα可提高免疫治疗药物的递送效率，为黑色素瘤的治疗提供新途径。图11 FRα导致细胞生长的作用机制抗体发现服务 & 产品01羊驼免疫&骆驼免疫—自建现代化养殖农场02万亿级天然抗体库产品—轻松DIY科研抗体03配套产品—助您轻松搭建基因工程抗体平台关于仁域生物成都仁域生物成立于2019年1月，是一家专注基因工程抗体技术和天然抗体库开发的公司，拥有优化的噬菌体展示抗体库技术和现代化的骆驼/羊驼养殖免疫基地。可为客户提供14天、100%成功率的先导抗体分子发现服务，彻底解决传统抗体定制的周期长、失败率高、成本高三大难题。目前已经成功完成300+靶点抗体筛选项目！protocol 获取 / 产品咨询邮箱｜find@renyubio.com电话｜19136178673地址｜成都市经开区科技产业孵化园关注我们，小编将持续更新相关内容～参考文献Liu Y, Chen X, Evan T, Esapa B, Chenoweth A, Cheung A, Karagiannis SN. Folate receptor alpha for cancer therapy: an antibody and antibody-drug conjugate target coming of age. MAbs. 2025 Dec;17(1):2470309. Ferrari FA, Ceccaroni M, Scambia G, Fagotti A, Pavone M, Bourdel N, Francesco R, Bogani G. Enhancing surgical precision in ovarian cancer with FRα-fluorescence-guided surgery. Eur J Surg Oncol. 2025 May 2;51(8):110120.Kong B, Zheng W. Mirvetuximab soravtansine: current and future applications. J Hematol Oncol. 2025 Mar 18;18(1):33. Bukowski K, Rogalska A, Marczak A. Folate Receptor Alpha-A Secret Weapon in Ovarian Cancer Treatment? Int J Mol Sci. 2024 Nov 6;25(22):11927. Gonzalez T, Muminovic M, Nano O, Vulfovich M. Folate Receptor Alpha-A Novel Approach to Cancer Therapy. Int J Mol Sci. 2024 Jan 15;25(2):1046. Kokori E, Olatunji G, Komolafe R, Abraham IC, Ukoaka B, Samuel O, Ayodeji A, Ogunbowale I, Ezenwoba C, Aderinto N. Mirvetuximab soravtansine: A breakthrough in targeted therapy for platinum-resistant ovarian cancer. Medicine (Baltimore). 2024 May 17;103(20):e38132.Mai J, Wu L, Yang L, Sun T, Liu X, Yin R, Jiang Y, Li J, Li Q. Therapeutic strategies targeting folate receptor α for ovarian cancer. Front Immunol. 2023 Aug 30;14:1254532. Varaganti P, Buddolla V, Lakshmi BA, Kim YJ. Recent advances in using folate receptor 1 (FOLR1) for cancer diagnosis and treatment, with an emphasis on cancers that affect women. Life Sci. 2023 Aug 1;326:121802.Young O, Ngo N, Lin L, Stanbery L, Creeden JF, Hamouda D, Nemunaitis J. Folate Receptor as a Biomarker and Therapeutic Target in Solid Tumors. Curr Probl Cancer. 2023 Feb;47(1):100917. Nawaz FZ, Kipreos ET. Emerging roles for folate receptor FOLR1 in signaling and cancer. Trends Endocrinol Metab. 2022 Mar;33(3):159-174.

核酸药物

2018-08-29

·BioSpace

TapImmune to Participate at Two Upcoming September 2018 Industry Conferences

JACKSONVILLE, Fla., Aug. 29, 2018 /PRNewswire/ -- TapImmune Inc.(NASDAQ: TPIV), a clinical-stage immuno-oncology company, today announced that its President and CEO, Peter L. Hoang, will participate at two upcoming industry conferences. Mr. Hoang will present and participate in a panel discussion at the Hanson Wade CAR-TCR Summit, to be held September 4-7, 2018, in Boston, Massachusetts, and present at BioCentury's 25th Annual NewsMakers in the Biotech Industry to be held September 7, 2018, in New York City. CAR-TCR Summit Details: Date: Wednesday, September 5, 2018 Location: Cityview Room; Seaport Hotel and World Trade Center, Boston, MA Time: 2:25pm (ET): Company Presentation 5:15pm (ET): Panel - How to Make CAR/TCR Therapies Work Beyond the CD19/ALL Paradigm BioCentury Newsmakers Presentation Details: Date: Friday, September 7, 2018 Location: Millennium Broadway Hotel & Conference Center, New York City, NY Time: 2:30pm (ET): Presentation - Room 302/303 3:00pm (ET): Breakout Session - Room 301 Webcast: Available at About TapImmune Inc. TapImmune Inc. is a leader in the development of novel immunotherapies for cancer, with multiple Phase 2 and Phase 1b/2 clinical studies currently ongoing for the treatment of ovarian and breast cancer. The Company's peptide or nucleic acid-based immunotherapeutic products comprise multiple naturally processed epitopes (NPEs) that are designed to comprehensively stimulate a patient's killer T cells and helper T cells, and to restore or further augment antigen presentation using proprietary nucleic acid-based expression systems. This unique approach can produce off-the-shelf T cell vaccine candidates that elicit a broad-based T cell response and can be used without respect to HLA type. The Company's technologies may be used as stand-alone medications or in combination with other treatment modalities. TapImmune has announced a proposed merger with Marker Therapeutics, Inc., a privately-held clinical stage developer of a transformative, non-genetically engineered, multi-antigen T cell therapy platform, which will add a significant portfolio of clinical-stage cell therapies to create a leading immuno-oncology pipeline. For additional information, please visit: To receive future press releases via email, please visit: Follow us on Twitter @Tapimmune_Inc, or follow us on Facebook. For answers to frequently asked questions, please visit our FAQs page: Forward-Looking Statement Disclaimer This release contains forward-looking information within the meaning of the Private Securities Litigation Reform Act of 1995. Statements in this news release concerning the Company's expectations, plans, business outlook or future performance, and any other statements concerning assumptions made or expectations as to any future events, conditions, performance or other matters, are "forward-looking statements". Forward-looking statements are by their nature subject to risks, uncertainties and other factors which could cause actual results to differ materially from those stored in such statements. Such risks, uncertainties and factors include, but are not limited to the results of the Phase 2 clinical trials, the ability to obtain regulatory approval of TPIV200, the Company's ability to raise future financing for continued development and the ability to successfully commercialize TPIV200 as well as the risks and uncertainties set forth in the Company's most recent Form 10-K, 10-Q and other SEC filings which are available through EDGAR at The Company assumes no obligation to update the forward-looking statements. View original content with multimedia: SOURCE TapImmune Inc. Company Codes: NASDAQ-SMALL:TPIV

细胞疗法疫苗并购

100 项与 Folate receptor alpha vaccine(Mayo Clinic) 相关的药物交易

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适应症	最高研发状态	国家/地区	公司	日期
卵巢子宫内膜样癌	临床2期	美国	Mayo Clinic	2024-11-08
输卵管透明细胞腺癌	临床2期	美国	Mayo Clinic	2024-11-08
高级别输卵管浆液性腺癌	临床2期	美国	Mayo Clinic	2024-11-08
卵巢高级别浆液性腺癌	临床2期	美国	Mayo Clinic	2024-11-08
卵巢腺癌	临床2期	美国	Mayo Clinic	2024-11-08
卵巢癌肉瘤	临床2期	美国	Mayo Clinic	2024-11-08
原发性腹膜透明细胞癌	临床2期	美国	Mayo Clinic	2024-11-08
原发性腹膜子宫内膜样腺癌	临床2期	美国	Mayo Clinic	2024-11-08
原发性腹膜高级别浆液性腺癌	临床2期	美国	Mayo Clinic	2024-11-08
铂敏感性卵巢癌	临床2期	美国	Marker Therapeutics, Inc.	2017-07-20

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT02978222 (Pubmed) 人工标引	临床2期	卵巢癌	120	TPIV200receptor-alpha peptides (TPIV200 + GM-CSF)	蓋淵鏇範淵鏇遞壓淵糧(鑰簾選鬱鑰膚選憲襯顧) = 夢鬱鹹夢淵憲簾夢廠膚願壓廠積範鹹餘餘簾蓋 (顧壓鬱構選膚齋窪簾顧 )	不佳	2024-10-01
				GM-CSF alone	蓋淵鏇範淵鏇遞壓淵糧(鑰簾選鬱鑰膚選憲襯顧) = 鹽積窪醖憲鑰鏇觸衊廠願壓廠積範鹹餘餘簾蓋 (顧壓鬱構選膚齋窪簾顧 )
NCT02978222 (NCT02978222 \| ###DELETE, CTgov)	临床2期	铂敏感性卵巢癌	120	FRα peptide plus Adjuvant (GM-CSF) (FRα Peptide Plus Adjuvant (GM-CSF))	顧網簾鹽鑰積醖窪憲願(願製鑰願憲製糧衊廠鑰) = 獵窪顧遞範醖願鹹範廠顧鏇窪簾膚淵鏇選築網 (齋鑰鹹齋廠艱鑰膚鹽製, 齋簾網築獵繭淵獵願鏇 ~ 簾廠鹽鏇獵夢範觸顧鑰) 更多	-	2022-12-15
				GM-CSF (Adjuvant (GM-CSF) Alone)	顧網簾鹽鑰積醖窪憲願(願製鑰願憲製糧衊廠鑰) = 繭遞鏇淵齋襯選鹹衊憲顧鏇窪簾膚淵鏇選築網 (齋鑰鹹齋廠艱鑰膚鹽製, 簾鑰襯遞壓鏇衊範齋願 ~ 鑰鑰壓廠獵蓋願願壓簾) 更多
NCT02764333 (CTgov)	临床2期	铂耐药性卵巢癌	29	TPIV200+Durvalumab	醖憲選壓簾築壓廠製餘 = 範鏇淵遞壓範齋網鹽遞鏇醖願夢獵顧窪鹹鑰顧 (鏇蓋鏇窪壓窪觸糧鏇廠, 憲範鬱築範窪範衊範鏇 ~ 鹹願願膚齋網齋糧鑰構) 更多	-	2021-11-30
NCT02764333 (Pubmed \| J Immunother Cancer) 人工标引	临床2期	卵巢癌	27	durvalumab+TPIV200	網膚襯鬱製製衊築簾憲(鏇網鹹網膚蓋顧衊壓醖) = 簾遞蓋鬱範膚範觸蓋鏇選範艱構艱衊構範觸憲 (憲網壓鬱襯繭襯憲遞獵 ) 更多	积极	2020-06-01
NCT02978222 (ASCO 12020 \| ASCO 22020) 人工标引	临床2期	卵巢癌	120	FRα peptides+GM-CSF	糧夢願糧構鹹糧鑰鬱鑰(淵顧醖遞艱齋觸艱鹹鑰) = 積憲網醖夢衊夢醖製醖網願壓壓壓廠醖構製網 (積鏇夢選淵廠鑰鹽壓鹽 ) 更多	不佳	2020-05-25
				GM-CSF	糧夢願糧構鹹糧鑰鬱鑰(淵顧醖遞艱齋觸艱鹹鑰) = 顧襯簾襯餘糧簾襯願範網願壓壓壓廠醖構製網 (積鏇夢選淵廠鑰鹽壓鹽 ) 更多