PMB-CT01 (BAFFR-CAR T cell) therapy to examine preliminary safety and clinical responses in patients with B-cell malignancies who are ineligible for or failed CD19-directed therapy, including CD19-negative disease.

作者: Espinosa, Ruby ; Baird, John H. ; Wang, Xiuli ; Cheng, Hazel (Ting-Ying) ; Barva, Baishakhi ; Puverel, Sandrine ; Kim, Teresa ; Guan, Min ; Aldoss, Ibrahim ; Del Real, Marissa ; Macias, Alan ; Chen, Lu ; Kwak, Larry W. ; Kambhampati, Swetha ; Dulan, Sylvia ; Forman, Stephen J. ; Tiemann, Katrin ; Budde, Lihua Elizabeth ; Song, Joo Y

6534 Background: CD19-targeted therapies have shown remarkable efficacy in patients with B-cell malignancies. However, relapse with CD19 loss as a mechanism of tumor escape is common and represents a serious challenge. Patients who are ineligible for or have failed prior CD19-directed therapy have limited salvage options and a very poor prognosis. The B-cell activating factor receptor (BAFF-R) is functionally expressed in B-cell acute lymphoblastic leukemia (B-ALL) and non-Hodgkin lymphomas (NHL), including in patients with CD19-negative relapse (Qin et al., Sci Transl Med. 2019). As a critical regulator of B-cell function and survival, BAFF-R may be less prone to downregulation by tumors as a mechanism of antigen escape. Methods: We are conducting two phase 1 clinical trials of BAFFR-CAR T cells in patients with relapsed/refractory (r/r) B-ALL (NCT04690595) and NHL (NCT05370430). Primary endpoints are dose limiting toxicities (DLTs) and all other toxicities. Secondary endpoints include response rate, minimal residual disease (MRD) negative rate, PFS and OS. Response is evaluated using European LeukemiaNet criteria for B-ALL and Lugano 2014 for NHL. Results: As of Feb. 1st, 2024, 1 B-ALL and 3 NHL patients have completed treatment and post-treatment evaluations. Each received 50M BAFFR CAR T cells (starting dose level in both trials). The B-ALL patient had CD19/CD20/CD22-negative disease, and had received prior blinatumomab. NHL patients #1 and #2 both had CD19-expressing mantle cell lymphoma (MCL) and had received prior CD19 CAR T cells. Patient #2 had also received a CD3/CD20 bispecific antibody. NHL patient #3 had CD19/CD20-negative T cell/histiocyte-rich large B-cell lymphoma (THRBCL) and had not received prior CD19 CAR T cells. There were no DLTs, all patients had Gr. 1 cytokine release syndrome, and 2/3 NHL patients had Gr. 1 immune effector cell-associated neurotoxicity syndrome. Robust CAR T cell expansion was seen in all patients with a peak on days 12-14 post-infusion. The B-ALL and the 2 MCL patients reached MRD-negative complete response (CR) at 1 month post-treatment. The THRBCL patient had partial response (PR) at 1 month that converted to CR at 3 months. The B-ALL patient successfully transitioned to allogeneic HCT while in CR at 3 months post-infusion. Responses are ongoing in all NHL patients at 14, 10, and 8 months for patients #1, #2 and #3, respectively. Additional patients have been enrolled at the next dose level (200M CAR T cells). Results for these patients will be presented at the meeting. Conclusions: With a 100% CR rate at 3 months in the first 4 patients and durable responses at dose level 1, BAFFR-CAR T cells are a promising therapeutic option for patients with r/r B-cell malignancies who are ineligible or failed prior CD19-targeted therapy, including with CD19 antigen loss. Clinical trial information: NCT04690595 , NCT05370430 .

2023-11-02·Blood

Promising Safety and Anti-Lymphoma Efficacy of Autologous Pmb-CT01 (BAFFRCAR T Cell) Therapy in a First-in-Human Phase 1 Study

作者: Barva, Baishakhi ; Baird, John H. ; Chen, Lu ; Macias, Alan ; Tiemann, Katrin ; Kwak, Larry W. ; Puverel, Sandrine ; Del Real, Marissa Morales ; Song, Joo Y. ; Cheng, Hazel Ting-Ying ; Budde, L. Elizabeth ; Forman, Stephen J. ; Kambhampati, Swetha ; Dulan, Sylvia ; Kim, Teresa

Introduction: CD19 chimeric antigen receptor (CAR) T cell therapy has revolutionized the treatment landscape of B cell lymphoma. However, a significant number of patients with aggressive B cell lymphoma (aBCL), mantle cell lymphoma (MCL) and follicular lymphoma (FL) still relapse or have refractory disease after autologous CD19CAR T cell therapy, highlighting the urgent unmet need to seek alternative approaches to improve the outcomes. BAFF-R signaling is considered a driver of B cell and malignant growth and survival. This feature may limit the capacity of B cell tumors to evade therapy by loss of BAFF-R expression. Recent work (Qin et al., Sci Transl Med. 2019) has shown that BAFF-R expression is independent of CD19 expression on malignant B cells and that CAR T cells targeting BAFF-R were able to effectively eliminate various B cell malignancies in the preclinical setting. Here we report the initial results from the first 3 patients treated on an ongoing phase 1, first-in-human clinical trial (NCT05370430) evaluating the safety and efficacy of autologous BAFFRCAR T cells in patients with B cell lymphoma.Study Design and Methods: Our studyis a phase 1, single center, open label, therapeutic trial. PMB-CT01 is a T N/ SCM-enriched BAFFR.41BB.z.EGFRt-CAR T cell therapy which was previously described (Qin et al. Sci Transl Med. 2019). There are 3 dose levels (DL) in the dose escalation phase including 50x10 6 (DL1), 200x10 6 (DL2), and 600x10 6 (DL3) CAR T cells. The lymphodepletion regimen consists of cyclophosphamide 500 mg/m 2/day and fludarabine 30 mg/m 2/day for 3 days.The primary endpoints are the incidence of adverse events and the determination of the maximum tolerated dose. Secondary endpoints include disease response, incidence of negative minimal residual disease (MRD), progression-free survival, and overall survival. ASTCT consensus criteria are used to grade cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). Responses are determined by Lugano 2014 (Cheson et al., JCO 2014).Results: As of July 19, 2023, three patients were enrolled and all received treatment at DL1, 50x10 6 PMB-CT01(BAFFRCAR T cells). The median age was 56 years old (41-75), 100% male. Patients #1 and #2 had MCL and both had received prior treatment with BTK inhibitors, and progressed after CD19CAR T cell therapy. Both patients had bone marrow involvement prior to treatment, and had 4 and 10 prior lines of therapy, respectively. Patient #3 with T cell/histiocyte-rich B cell lymphoma had received 3 prior lines of therapy and his lymphoma was negative for both CD19 and CD20. All 3 patients developed grade 1 CRS only. All CRS events resolved with 2 doses of tocilizumab given to patient #1 and 1 dose to patient #2. Patients #1 and #2 also developed grade 1 ICANS which were self-limited and resolved without pharmacologic intervention. No dose-limiting toxicity (DLT) was observed. Infection was seen in patient #2 with viral pneumonia at month 3.All 3 treated patients responded to treatment. The overall response rate was 100% including MRD-negative complete response (CR) by flow cytometry and next-generation sequencing (NGS) in patient #1 and by flow cytometry in patient #2, and partial response (PR) in patient #3. All responses are ongoing at 8 months (patient #1), 4 months (patient #2) and 1.5 months (patient #3), respectively. Figure 1 shows the clearance of lymphoma cells in the bone marrow of the first patient 28 days post- CAR T cell infusion. Robust CAR T cell expansion was observed in all 3 patients with peak of expansion (between 2.1x10 6 and 8.9x10 6 copies/ml of blood) on day 12 (patient #1) and day 14 (patients #2 and #3) (Figure 1).Conclusions: PMB-CT01(BAFFRCART cell) treatment at DL1 was safe and demonstrated potent anti-lymphoma activity with a 100% ORR (2 CR, 1 PR) in patients with poor prognosis. CRS and ICANS were all grade 1 and reversible.Enrollment is ongoing at DL2, and additional clinical and correlative analyses will be presented at the meeting.

项与 PeproMene Bio, Inc. 相关的新闻（医药）

2024-10-28

·药研网

BAFF-APRIL系统：自免、肿瘤领域潜力无限

BAFF（B细胞激活因子,也称为TNFSF13B、CD257、BLys）和APRIL（增殖诱导配体，也称为CD256，TNFSF13）参与了许多人类自身免疫性疾病的发生，在系统性红斑狼疮(SLE)、IgA肾病、Sjögren’s综合征和类风湿关节炎患者的血清中检测到这些细胞因子水平升高。因此，这两种分子都是B细胞驱动的自身免疫性疾病的合理治疗靶点，一些BAFF/APRIL的抑制剂已经在临床试验中取得成功并获批上市。其中包括BAFF抑制剂贝利尤单抗和BAFF/APRIL双靶抑制剂泰它西普。 BAFF/APRIL系统概述 BAFF和APRIL都属于B细胞刺激因子，是维持B细胞和体液免疫的关键因素。 BAFF属于肿瘤坏死因子（TNF）配体家族成员，表达于单核细胞、树突状细胞及T细胞等表面。BAFF也可以从细胞表面分离，进入血液中形成可溶性分子。 BAFF 主要通过与B细胞表面的三种受体结合发挥作用，分别是：BAFFR(BAFF受体，也被称为BR3和TNF受体超家族成员13C)，TACI(钙调和亲环素配基相互作用因子，也称为TNF受体超家族成员13B)，BCMA(B细胞成熟抗原，也称为TNF受体超家族成员17)。 BAFF通过与其受体的结合在支持B细胞的存活和增殖、调节类别转换重组以及自身免疫性B细胞的选择等方面发挥关键作用；此外，有研究发现BAFF也能促进T细胞的活化、增殖和分化。 APRIL 和BAFF具有结构相似性，都是属于肿瘤坏死因子（TNF）超家族的成员。与BAFF不同，APRIL仅与TACI和BCMA（而非BAFF-R）结合以调节B细胞的功能和存活，并促进其分化为浆细胞。在健康人组织中，APRIL的表达相对较弱，而在肿瘤组织中却高表达。APRIL有两种生物活性存在形式，分别是以17k相对分子质量存在的可溶型和30k相对分子质量存在的膜结合型。研究显示，BAFF相对于APRIL对BAFF-R的结合有更强的特异性，但BCMA对APRIL的亲和力更高。图1.BAFF与BAFFR的配体受体结合图（DOI：10.1038/ng0805-793） BAFF-APRIL系统的临床价值 01 BAFF/BAFFR BAFF及其受体BAFFR在B细胞的生理和病理过程中发挥关键作用，针对这两个分子的靶向治疗已经成为自身免疫性疾病和相关恶性疾病的一种有效策略。 BAFF与BAFFR的结合能激活多个信号通路，包括NF-κB和PI3K，这些信号通路在B细胞存活和增殖中发挥重要作用。 BAFF和BAFFR的相互作用在临床上被用作治疗靶点。例如，贝利尤单抗（Benlysta）是针对BAFF的单克隆抗体，已被批准用于治疗系统性红斑狼疮等疾病。此外，针对BAFFR的靶向药物也在开发中，显示出治疗慢性淋巴细胞白血病和其他B细胞相关淋巴瘤潜力。迄今为止，全球尚未有针对BAFF-R的靶向药物获监管机构批准应用于临床治疗。图2.BAFF-BAFFR靶点全球在研项目汇总吉满生物自主研发，推出一系列BAFF和APRIL系统相关靶点的稳定过表达细胞系、报告基因检测细胞系、抗体及蛋白相关产品，充分满足药物研发需求，助力药物临床申报。详情咨询吉满客服联系同微信：18916119826！ Ianalumab Ianalumab是一种抗BAFF-R的单克隆抗体，在治疗干燥综合征和系统性红斑狼疮的2期临床试验中均获得积极结果，目前正在3期临床试验中接受检验。 PMB-101 PMB-CT01是一种潜在“first-in-class”的BAFFR靶向自体CAR-T细胞疗法。临床前研究发现，这种CAR-T细胞疗法能在体外和动物模型中杀死人类淋巴瘤和白血病细胞。2024年1月19日，PeproMene Bio宣布，其PMB-CT01在治疗复发/难治性急性B淋巴细胞白血病（r/r B-ALL）的1期临床试验中获得积极结果。第1队列首例患者在治疗后一个月得到完全缓解。 AUR200 AUR200 是一种高效、特异性的 BAFF 和 APRIL 活性免疫调节剂，AUR200 的作用机制已得到证实。Aurinia于2024年第三季度启动了AUR200的1期单剂量（SAD）研究。SAD研究的数据，包括安全性、耐受性、药代动力学和生物标志物，预计将于2025年上半年公布。 ESG206 诗健生物同类首创抗BAFF-R单克隆抗体ESG206，可通过抗体依赖的细胞介导的细胞毒性作用（ADCC）发挥肿瘤细胞杀伤效能。通过糖基化修饰使得ESG206无岩藻糖基化糖型的含量大大提高从而显著增强体外的ADCC作用。 ESG206拟应用于B细胞淋巴瘤和慢性淋巴细胞白血病，特别是对现有治疗耐药的B淋巴细胞瘤。目前该管线在中国和澳大利亚的临床申请均已获批。此外，ESG206后续还将开展自身免疫疾病治疗的开发和探索。安博泰克JH013注射液 8 月 2 日，安博泰克公司治疗自身免疫性疾病的抗BAFF-R单克隆抗体JH013注射液获得国家药品监督管理局颁发的临床研究（IND），这是首个获得临床研究批件的国产BAFF-R单克隆抗体。临床前研究证实，JH013 可以从蛋白水平及细胞水平与人BAFF-R呈线性结合，并且阻断 BAFF-R 与 BAFF 的相互作用，从而抑制 BAFF 引起的 B 淋巴细胞增殖。 023 TACI TACI作为BAFF的受体，其作用不局限于B细胞的生存和功能调节，还在T细胞的活化和成熟中发挥重要的交互调控作用。 BAFF与TACI之间的相互作用在多种自身免疫疾病（例如系统性红斑狼疮、类风湿性关节炎等）中被认为是病理机制的重要组成部分。近几年来，TACI靶点迅速变得火热，围绕该靶点，研发进展靠前的药物有Vera的Atacicept，荣昌生物的Telitacicept，Alpine的Povetacicept 等。 Vera：Atacicept Atacicept是可溶性全人源化的 TACIFc 融合蛋白，可与 BAFF 和 APRIL 这 2 种配体结合。Vera Therapeutics引进之后，Atacicept的临床开发重新走上正轨，目前IgA肾病三期临床正在进行，狼疮性肾炎、系统性红斑狼疮计划推进到三期临床，后续还有多个适应症处在早期临床阶段。荣昌生物：Telitacicept 泰它西普（Telitacicept，商品名：泰爱）是荣昌生物自主研发的靶向 BLyS 和 APRIL 的原创性抗体融合蛋白药物，用于治疗系统性红斑狼疮、类风湿性关节炎等多种自身免疫疾病。 2021年3月，泰它西普在中国附条件获批上市，治疗系统性红斑狼疮，成为全球首款TACI-Fc新药。 Alpine：Povetacicept Povetacicept目前进展最快的为IgA肾病，今年下半年将启动三期关键临床，后续探索的适应症还有系统性红斑狼疮、膜性肾病、血球减少症。 03 BCMA BCMA可分别与BAFF或APRIL两种配体相结合。其主要功能是调节B细胞的生存和成熟。在多发性骨髓瘤细胞中，BCMA的过度表达与疾病的恶性转化过程密切相关，是用于治疗多发性骨髓瘤（MM）的一个重要靶点。近年来，针对BCMA的不同类型免疫治疗药物得到了广泛的开发，主要分为三类：嵌合抗原受体T细胞（CAR-T）疗法、双特异性抗体（BsAb）和抗体药物偶联物（ADC）。（1）CAR-T细胞疗法 CAR-T细胞疗法是目前针对BCMA的最活跃的研发领域之一。此类疗法通过对患者T细胞进行基因工程修饰，使其表达对BCMA特异的CAR，能够识别并攻击表达BCMA的肿瘤细胞。目前已有多个BCMA靶向CAR-T细胞疗法获得审批，如百时美施贵宝的Abecma和强生的Cilta-cel，这些疗法在复发或难治性多发性骨髓瘤患者中显示出显著疗效。（2）双特异性抗体（BsAb）双特异性抗体通过同时结合BCMA和T细胞表面抗原，使这两种细胞相互靠近，增强T细胞对肿瘤细胞的杀伤能力。此类药物的代表有Teclistamab，它是第一个获得FDA批准的靶向BCMA的双特异性抗体，也是是全球首个BCMA/CD3双特异性抗体，针对复发或难治性多发性骨髓瘤患者。（3）抗体药物偶联物（ADC）抗体药物偶联物则是将抗体与细胞毒性药物结合，通过靶向BCMA直接将药物传递至恶性浆细胞。这类药物例如Belantamab mafodotin（Blenrep），在FDA批准后显著改善了多发性骨髓瘤的治疗效果。 04 APRIL APRIL主要在B细胞和浆细胞中表达，可以结合TACI和BCMA，从而影响B细胞的增殖和分化。特别是APRIL在自身免疫性疾病中，通过促进自身抗体的产生，起到了重要的病理角色。 APRIL的靶点药物开发近年来受到了广泛关注，特别是在自身免疫性疾病和某些肿瘤治疗领域。目前进展最快的是大冢制药的Sebeprenlimab（VIS649），它是一款抗APRIL单抗。10月22日，大冢制药宣布Sebeprenlimab治疗IgA肾病的三期临床VISIONARY达到预设主要终点，经过9个月治疗24小时uPCR（尿蛋白肌酐比）显著下降，安全性与此前报道的数据一致。总结总的来说，BAFF和APRIL系统相关的靶向药物，未来临床应用前景广阔，尤其是在自身免疫疾病和肿瘤免疫治疗领域。正在进行的临床研究将进一步验证这些生物制剂的长期疗效和安全性，尤其是在不同患者群体中的应用效果。我们期待能为治疗相关疾病提供新的策略。用心做好细胞，为更好的靶向药吉满生物自主研发，推出一系列BAFF和APRIL系统相关靶点的稳定过表达细胞系、报告基因检测细胞系、抗体及蛋白相关产品，充分满足药物研发需求，助力药物临床申报。吉满优势高稳定性：我们的稳转细胞株经过严格筛选，确保在长期培养中保持高稳定性，适合大规模生产和长期实验使用纯度和活性：我们的蛋白、抗体产品经过高效纯化，确保高纯度和生物活性，适合用于基础研究、药物开发和临床前研究定制服务：我们提供个性化的定制服务，根据客户的具体需求，开发特定的细胞株、抗体和蛋白，满足不同研究领域的需求技术支持：我们的专业团队提供全面的技术支持和咨询服务，帮助客户解决在使用产品过程中遇到的各种问题可靠性和信誉：我们在行业内拥有良好的声誉，客户反馈积极，产品质量和服务得到了广泛认可产品列表数据展示（部分） GM-C25349:H_BCMA Reporter Cell Line 使用Recombinant Human APRIL(N-Flag-His)(novoprotein/CU89)蛋白激活验证使用Recombinant Human APRIL (N-Flag-His) (novoprotein/CU89)蛋白激活后，在分别使用Anti-BCMA hIgG1 Antibody(SEA-BCMA)、Anti-BCMA hIgG1 Antibody(Belantamab) 抗体block验证 GM-C31635:H_BAFFR Reporter Cell Line 使用Human BAFF Protein; His Tag蛋白激活验证使用Human BAFF Protein激活后，在使用Anti-BAFF hlgG1 Antibody(belimumab)抗体block验证结果 GM-C35041:H_TACI Reporter Cell Line 使用Human BAFF Protein; His Tag蛋白激活验证使用Human BAFF Protein; His Tag蛋白激活后，在使用Anti-BAFF hlgG1 Antibody(belimumab)抗体Block验证结果 GM-C24849:H_BCMA CHO-K1 Cell Line 使用Anti-BCMA hIgG1 Antibody(Belantamab) 抗体流式验证结果 GM-C24896:H_BCMA HEK-293 Cell Line 使用Anti-BCMA hIgG1 Antibody(Belantamab) 抗体流式验证结果 GM-C24899:Cynomolgus_BCMA CHO-K1 Cell Line 使用Anti-BCMA hIgG1 Antibody(Belantamab) 抗体流式验证结果联系我们吉满生物助力药物研发，紧随前沿靶点资讯，储备几百株现货细胞，覆盖GPCR、细胞因子、免疫检查点、TAA等多领域，截止当前已布局近500个热门靶向药靶点，1000余株细胞系，旨在助力、加速大分子早期研发，做到进口细胞的国产替代。同时可根据客户需求提供细胞系服务。扫码咨询扫码找现货

ASH会议临床1期上市批准临床结果引进/卖出

2024-08-08

·美通社

PeproMene Bio宣布的一项研究表明，新型嵌合抗原受体（CAR）T细胞具有强大多功能性

CAR T 细胞疗法的多功能性与患者持续18 个月的缓解期相关加利福尼亚州尔湾 2024年8月9日 /美通社/ -- 作为一家临床阶段的生物技术公司， PeproMene Bio, Inc. 致力于开发治疗癌症和免疫疾病的新疗法。该公司今天宣布，City of Hope开发的BAFF-R CAR T（即PMB-CT01）显示具有优于CD19 CAR T细胞的多功能性，CD19 CAR T细胞用于目前美国食品药品监督管理局批准的CAR T细胞疗法。该发现基于一项相关性研究，已发表在《Blood Advances》期刊上。研究人员利用单细胞平台发现，PMB-CT01 CAR T细胞比CD 19 CAR T细胞具有更强的多功能性，即T细胞能够同时执行多种功能。 PMB-CT01细胞还产生了更多的刺激性细胞因子（可刺激免疫系统）和效应细胞因子（可直接杀死癌细胞）。研究人员利用City of Hope开发的测定方法，对一名57岁套细胞淋巴瘤复发男性患者的BAFF-R CAR T细胞产品进行了测试。该患者之前接受过CD19 CAR T细胞疗法，但没有达到缓解效果。在City of Hope使用PMB-CT01进行的 1期临床试验中，这名男子接受了一次输液治疗，副作用极小，此后18个月内病情完全缓解，通过敏感的微小残留病分子检测，仍检测不到癌症。该研究报告了强有力的多功能性指标，这些指标与输注后CAR T细胞的成功扩增和患者的持续缓解相关。研究人员计划利用该测定方法，对参与试验的其他五名患者进行CAR T细胞产品的测试，这些患者也有与PMB-CT01相似的缓解经历。 City of Hope综合癌症中心副总裁兼副主任、PeproMene科学创始人兼科学顾问委员会受薪主席 Larry W. Kwak 博士表示："我们研发的BAFFR-CAR T细胞疗法，为许多在接受商业CD19 CAR T细胞疗法后的淋巴瘤和白血病复发患者提供了另一种治疗方案，目前的研究结果展示了以最小的毒性实现理想的最大疗效。" Kwak持有PeproMene的股权。他还说："我们已为CAR T细胞产品开发出一种强大且可靠的多功能测定方法，这不仅能预测患者反应，还能加快有效CAR T细胞疗法的研发进程。" 作为该试验的首席研究员、血液学和造血细胞移植学科副教授，以及City of Hope免疫效应细胞治疗项目执行医学主任，Elizabeth Budde博士于2023年12月在美国血液学会的会议上提交了初步试验结果。 "令人兴奋的是，五名非霍奇金淋巴瘤患者和一名B细胞急性淋巴细胞白血病患者接受了PMB-CT01治疗，他们100%表现出持久的反应。"Budde博士表示， "许多试验患者在接受CD19 CAR T疗法后复发和/或呈现CD19阴性。 PMB-CT01可以为其他也面临这种困境的患者提供可行的选择。" PeproMene Bio首席运营官Hazel Cheng博士则表示："该测定方法可用于当前和未来的临床试验，以指导PMB-CT01的开发。 PeproMene将继续致力于这种具有潜在前景的新型细胞疗法的科学和临床开发。" 关于PMB-CT01 PMB-CT01是一种首创的靶向BAFF-R、自体CAR T细胞疗法。 BAFF-R（ B-细胞活化因子受体）是肿瘤坏死因子（TNF）受体超家族的成员，作为BAFF的主要受体，几乎专门在B细胞上表达。由于BAFF-R信号能促进正常B细胞的增殖，且似乎对B细胞存活至关重要，肿瘤细胞不太可能因缺失BAFF-R抗原而逃避治疗。凭借这种独特的特性，BAFFR CAR T疗法成为治疗B细胞恶性肿瘤的一种极有前景的方案。 BAFFR CAR由抗BAFF-R单链片段可变（scFv）抗体和第二代信号域CD3ζ和4-1BB构建而成。我们的研究表明，BAFFR-CAR T细胞在体外和动物模型中能够有效杀死人类淋巴瘤和白血病细胞。 PeproMene Bio已从City of Hope获得PMB-CT01的知识产权许可。关于PeproMene Bio 作为一家位于加利福尼亚州尔湾的临床阶段生物技术公司，PeproMene Bio, Inc.致力于开发治疗癌症和免疫疾病的新疗法。 PeproMene的主要候选药物PMB-CT01（BAFFR-CAR T细胞）目前正在1期临床试验中，用于治疗复发和难治性B细胞急性淋巴细胞白血病（B-ALL；NCT04690595）和B细胞非霍奇金淋巴瘤（B-NHL；NCT05370430）。 PeproMene Bio还在着手开发BAFFR双特异性T细胞衔接器和BAFFR-CAR NK细胞。联系人：John Fry， john.fry@pepromenebio.com

细胞疗法临床1期免疫疗法ASH会议

2024-08-07

·PRNewswire

PeproMene Bio announced study demonstrating strong polyfunctionality of novel chimeric antigen receptor (CAR) T cells

Polyfunctionality correlates with a patient's remission lasting over 18 months with the CAR T cell therapy IRVINE, Calif., Aug. 7, 2024 /PRNewswire/ -- PeproMene Bio, Inc., a clinical-stage biotech company developing novel therapies for cancers and immune disorders, today announced that City of Hope-developed BAFF-R CAR T, known as PMB-CT01, demonstrated better polyfunctionality than CD19 CAR T cells, which are used in current Food and Drug Administration-approved CAR T cell therapies, according to a correlative study published in Blood Advances. Researchers used a single-cell platform, which found that PMB-CT01 CAR T cells, had more polyfunctionality, which is T cells' ability to perform several functions at the same time, than CD 19 CAR T cells. PMB-CT01 cells also produced more stimulatory cytokines, which can spur the immune system, and effector cytokines, which can directly kill cancer cells. Using the City of Hope-developed assay, researchers tested a BAFF-R CAR T cell product from a 57-year-old man with relapsed mantle cell lymphoma. The patient had not achieved remission with prior CD19 CAR T cell therapies. After receiving one infusion in City of Hope's Phase 1 trial using PMB-CT01 and experiencing minimal side effects, the man has been in complete remission over 18 months and continues to have undetectable cancer by sensitive molecular tests for minimal residual disease. The study reported robust indicators of polyfunctionality, which correlated with successful CAR T cell expansion post-infusion and the patient's ongoing remission. Researchers plan to use the assay to test CAR T cell products from five other patients in the trial, all of whom have experienced similar remissions to PMB-CT01. "We developed BAFFR-CAR T therapy as another treatment option for a significant number of patients with lymphomas and leukemias who relapse after receiving commercial CD19 CAR T cell therapy, and our results so far represent the ideal maximal efficacy with minimal toxicity," said Larry W. Kwak, M.D., Ph.D., vice president and deputy director of City of Hope's Comprehensive Cancer Center and PeproMene's scientific founder and compensated chair of its Scientific Advisory Board. Kwak has an equity interest in PeproMene. "We have developed a robust and reliable polyfunctional assay for CAR T cell products, with the potential to predict patient outcomes and accelerate the development of effective CAR T cell therapies." Elizabeth Budde, M.D., Ph.D., the trial's principal investigator, an associate professor of hematology and hematopoietic cell transplantation and the executive medical director for the Immune Effector Cell Therapy Program at City of Hope, presented initial trial results at the American Society of Hematology's conference in December 2023. "It's exciting to say that five patients with non-Hodgkin lymphoma and one with B-cell acute lymphoblastic leukemia have been treated with PMB-CT01 and 100% have demonstrated durable responses," Dr. Budde said. "Many of the trial patients relapsed had after CD19 CAR T therapy and/or were CD19 negative. PMB-CT01 could present a viable option for other patients who also face this dilemma." "This assay can be applied to current and future clinical trials to guide the development of PMB-CT01. PeproMene remains committed to the ongoing scientific and clinical development of this potentially promising new cell therapy" said Hazel Cheng Ph.D., COO of PeproMene Bio. About PMB-CT01 PMB-CT01 is a first-in-class, BAFF-R-targeted, autologous CAR T cell therapy. BAFF-R (B- Cell Activating Factor Receptor), a member of the tumor necrosis factor (TNF) receptor superfamily, is the main receptor for BAFF and is expressed almost exclusively on B cells. Since BAFF-R signaling promotes normal B-cell proliferation and appears to be required for B-cell survival, tumor cells are unlikely to escape therapy via loss of the BAFF-R antigen. This unique characteristic makes BAFFR CAR T therapy a highly promising option for treating B-cell malignancies. The BAFFR CAR was constructed using anti-BAFF-R single-chain fragment variable (scFv) antibodies and second-generation signaling domains CD3ζ and 4-1BB. Our research has demonstrated that BAFFR-CAR T cells effectively kill human lymphomas and leukemias both in vitro and in animal models. PeproMene Bio has licensed the intellectual property of PMB-CT01 from City of Hope. About PeproMene Bio PeproMene Bio, Inc. is a clinical-stage biotech company in Irvine, California developing novel therapies to treat cancers and immune disorders. PeproMene's lead candidate, PMB-CT01 (BAFFR-CAR T cells) is currently being investigated to treat relapsed and refractory B-cell acute lymphoblastic leukemia (B-ALL; NCT04690595) and B-cell non-Hodgkin lymphoma (B-NHL; NCT05370430) in phase 1 clinical trials. PeproMene Bio is also developing BAFFR Bispecific T Cell Engager and BAFFR-CAR NK cells. Contact: John Fry, [email protected] SOURCE PeproMene Bio, Inc.

细胞疗法临床1期免疫疗法ASH会议临床结果

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药物(靶点)	适应症	全球最高研发状态

Anti-BAFF receptor CAR-T cell therapy (City of Hope National Medical Centre/PeproMene Bio) ( BAFF-R )	难治性B细胞淋巴瘤更多	临床1期
B Cell Malignancies(PeproMene)	慢性淋巴细胞白血病更多	临床前
BAFFRxCD3 BITE (Pepromene) ( BAFF-R x CD3 )	肿瘤更多	临床前
Autoimmune Disorders(Pepromene)	自身免疫性疾病更多	临床前
BAFFR靶向CAR-NK(PeproMene) ( BAFF-R )	肿瘤更多	临床前