Anti-CD3/anti-EGFR -activated T cells(Barbara Ann Karmanos Cancer Institute)(Anti-CD3/anti-EGFR -activated T cells(Barbara Ann Karmanos Cancer Institute))

概要

基本信息

药物类型

双特异性T细胞结合器

别名

EGFR BATs、EGFRBi-Armed Autologous T Cells(Barbara Ann Karmanos Cancer Institute)、anti-CD3 x anti-EGFR bispecific antibody (EGFRBi) armed activated T cells

靶点

CD3 x EGFR

作用方式

刺激剂、调节剂

作用机制

CD3刺激剂(T细胞表面糖蛋白CD3复合体刺激剂)、EGFR调节剂(表皮生长因子受体erbB1调节剂)

治疗领域

肿瘤消化系统疾病内分泌与代谢疾病

在研适应症

胰腺癌

非在研适应症

结肠癌神经胶质肉瘤大肠恶性肿瘤+ [2]

原研机构

Barbara Ann Karmanos Cancer Institute

在研机构

Barbara Ann Karmanos Cancer Institute

University of Virginia Foundation

非在研机构-

权益机构-

最高研发阶段临床2期

首次获批日期-

最高研发阶段(中国)-

特殊审评-

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关联

4

项与 Anti-CD3/anti-EGFR -activated T cells(Barbara Ann Karmanos Cancer Institute) 相关的临床试验

NCT03344250

/ Completed临床1期IIT

A Phase I Study Targeting Newly Diagnosed Glioblastoma with Anti-CD3 × Anti-EGFR Bispecific Antibody Armed T Cells (EGFR BATs) in Combination with Radiation and Temozolomide

This is a phase I trial using EGFR Bi-armed Activated T-cells (BATs) in combination with standard of care temozolomide (TMZ) and radiation (RT) in patients with glioblastoma (GBM). The purpose of the study is to determine a safe dose of EGFR BATs when given with standard of care therapy.

开始日期2018-03-01

申办/合作机构

University of Virginia

NCT03269526

/ Active, not recruiting临床1/2期IIT

Phase Ib/II Treatment of Advanced Pancreatic Cancer With Anti-CD3 x Anti-EGFR-Bispecific Antibody Armed Activated T-Cells (BATs)

This protocol will confirm toxicities and estimate the clinical efficacy of combining anti-CD3 x anti-EGFR bispecific antibody (EGFRBi) armed activated T cells (EGFR BATs) given to patients with locally advanced or metastatic pancreatic cancer who have received at least one dose of first line chemotherapy and may have responding, stable or progressive disease. Phase Ib will confirm a safe dose of 8 infusions, given twice weekly, of EGFR-BATs in 3 to 6 subjects. The phase II portion of the trial will test the clinical efficacy of this dose in 22 patients (including those in Phase Ib).

开始日期2017-07-28

申办/合作机构

University of Virginia

NCT02521090

/ Withdrawn临床1/2期IIT

Targeting Recurrent Glioblastoma With Anti-CD3 x Anti-EGFR Bispecific Antibody Armed T Cells: A Phase I/II Study

This phase I/II trial studies the side effects and best dose of epidermal growth factor receptor bispecific antibody (EGFRBi)-armed autologous T cells and how well it works in treating patients with glioblastoma that have come back or does not respond to treatment. EGFRBi-armed autologous T cells coated with antibodies (proteins used by the immune system to target and kill foreign objects such as cancer cells) may have great ability to seek out, attach to, and destroy glioblastoma cells.

开始日期2015-08-01

申办/合作机构

Barbara Ann Karmanos Cancer Institute

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100 项与 Anti-CD3/anti-EGFR -activated T cells(Barbara Ann Karmanos Cancer Institute) 相关的临床结果

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100 项与 Anti-CD3/anti-EGFR -activated T cells(Barbara Ann Karmanos Cancer Institute) 相关的转化医学

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100 项与 Anti-CD3/anti-EGFR -activated T cells(Barbara Ann Karmanos Cancer Institute) 相关的专利（医药）

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3

项与 Anti-CD3/anti-EGFR -activated T cells(Barbara Ann Karmanos Cancer Institute) 相关的文献（医药）

2024-01-01·Journal of Neuro-Oncology

Phase I study targeting newly diagnosed grade 4 astrocytoma with bispecific antibody armed T cells (EGFR BATs) in combination with radiation and temozolomide

Article

作者: Lopes, M Beatriz ; Kassay-McAllister, Jessica ; Schiff, David ; Le, Tri ; Fadul, Camilo E ; Donahue, Joseph ; Lum, Lawrence G ; Thakur, Archana ; Schalk, Dana ; Kim, Jungeun ; Purow, Benjamin ; Dillon, Patrick ; Liu, Qin

AbstractPurposeThe purpose of this study was to determine the safety, feasibility, and immunologic responses of treating grade 4 astrocytomas with multiple infusions of anti-CD3 x anti-EGFR bispecific antibody (EGFRBi) armed T cells (EGFR BATs) in combination with radiation and chemotherapy.MethodsThis phase I study used a 3 + 3 dose escalation design to test the safety and feasibility of intravenously infused EGFR BATs in combination with radiation and temozolomide (TMZ) in patients with newly diagnosed grade 4 astrocytomas (AG4). After finding the feasible dose, an expansion cohort with unmethylated O6-methylguanine-DNA methyltransferase (MGMT) tumors received weekly EGFR BATs without TMZ.ResultsThe highest feasible dose was 80 × 109 EGFR BATs without dose-limiting toxicities (DLTs) in seven patients. We could not escalate the dose because of the limited T-cell expansion. There were no DLTs in the additional cohort of three patients with unmethylated MGMT tumors who received eight weekly infusions of EGFR BATs without TMZ. EGFR BATs infusions induced increases in glioma specific anti-tumor cytotoxicity by peripheral blood mononuclear cells (p < 0.03) and NK cell activity (p < 0.002) ex vivo, and increased serum concentrations of IFN-γ (p < 0.03), IL-2 (p < 0.007), and GM-CSF (p < 0.009).ConclusionTargeting AG4 with EGFR BATs at the maximum feasible dose of 80 × 109, with or without TMZ was safe and induced significant anti-tumor-specific immune responses. These results support further clinical trials to examine the efficacy of this adoptive cell therapy in patients with MGMT-unmethylated GBM.ClinicalTrials.gov Identifier: NCT03344250

2021-01-01·OncoImmunology2区 · 医学

Priming of pancreatic cancer cells with bispecific antibody armed activated T cells sensitizes tumors for enhanced chemoresponsiveness

2区 · 医学

ArticleOA

作者: Tomaszewski, Elyse N. ; LaBrie, Timothy M. ; Schalk, Dana L. ; Schienschang, Amy ; Ung, Johnson ; Thakur, Archana ; Lum, Lawrence G.

In this study, we investigated the ability of bispecific antibody armed activated T cells to target drug resistant pancreatic cancer cells and whether or not "priming" these resistant cancer cells with bispecific antibody armed activated T cells could enhance subsequent responsiveness to chemotherapeutic drugs. Chemotherapeutic responses for pancreatic cancer are either limited or the tumors develop resistance to chemotherapy regimens. The impetus for this study was the remarkable clinical response seen in our earlier phase I/II clinical trial: a pancreatic cancer patient with drug resistant tumors who showed progression of disease following three infusions of anti-CD3 x anti-EGFR bispecific antibody armed activated T cells (EGFR BATs) was restarted on the initial low dose of 5-fluorouracil showed complete response, suggesting that BATs infusions may have sensitized patient's tumor for chemoresponsiveness. In the current study, we tested the hypothesis that BATs can sensitize tumors for chemoresponsiveness. Gemcitabine or cisplatin-resistant MiaPaCa-2 and L3.6 cell lines were effectively targeted by EGFR BATs. Priming of drug sensitive or resistant cells with EGFR BATs followed by retargeting with lower concentrations of 50% inhibitory concentration of gemcitabine or cisplatin showed enhanced cytotoxicity. Gemcitabine or cisplatin-resistant cell lines show an increased proportion of CD44⁺/CD24⁺/EpCAM⁺ cancer stem like cells as well as an increased number of ABC transporter ABCG2 positive cells compared to the parental cell lines. These data suggest that bispecific antibody armed activated T cells can target and kill chemo-resistant tumor cells and also markedly augment subsequent chemotherapeutic responsiveness, possibly by modulating the expression of ABC transporters.

2020-01-01·OncoImmunology2区 · 医学

Clinical and immune responses to anti-CD3 x anti-EGFR bispecific antibody armed activated T cells (EGFR BATs) in pancreatic cancer patients

2区 · 医学

ArticleOA

作者: Fields, Kristie ; Dufrense, Melissa ; Philip, Philip ; Schalk, Dana ; Deol, Abhinav ; Choi, Minsig ; Thakur, Archana ; Aon, Hussein D. ; Shields, Anthony F. ; Dyson, Gregory ; Kondadasula, Vidya ; Lum, Lawrence G.

Purpose This was a phase I/II adoptive T cell trial in 7 locally advanced and metastatic pancreatic cancer patients using 3-8 infusions of anti-CD3 x anti-EGFR bispecific antibody armed activated T cells (BATs) to determine safety, the maximum tolerated dose (MTD), immune responses, time to progression (TTP), and overall survival (OS). Study Design: T cells obtained by apheresis were expanded and armed with EGFRBi, cryopreserved for infusions. In a phase I dose escalation, five patients received three weekly infusions of 10-40 × 10⁹ BATs/infusion followed by a booster infusion 3 months later, and 2 patients received 8 infusions twice weekly for 4 weeks in a phase II. The trials were registered at http://www.clinicaltrials.gov, NCT01420874 and NCT02620865. Results: There were no dose-limiting toxicities (DLTs), and the targeted dose of 80 × 10⁹ BATs was met. The median TTP is 7 months, and the median OS is 31 months. Two patients had stable disease for 6.5 and 25+ months, and two patients developed complete responses (CRs) after restarting chemotherapy. Infusions of BATs induced anti-pancreatic cancer cytotoxicity, innate immune responses, cytokine responses (IL-12, IP-10), and shifts in CD4 and CD8 Vβ repertoire with enhanced cytoplasmic IFN-γ staining in the Vβ repertoire of the CD8 subset that suggest specific clonal TCR responses. Conclusions: Infusions of BATs are safe, induce endogenous adaptive anti-tumor responses, and may have a potential to improve overall survival.

100 项与 Anti-CD3/anti-EGFR -activated T cells(Barbara Ann Karmanos Cancer Institute) 相关的药物交易

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研发状态

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
神经胶质肉瘤	临床2期	-	Barbara Ann Karmanos Cancer Institute	2015-08-01
复发性胶质母细胞瘤	临床2期	-	Barbara Ann Karmanos Cancer Institute	2015-08-01
胰腺癌	临床2期	-	University of Virginia Foundation	-
胰腺癌	临床2期	-	Barbara Ann Karmanos Cancer Institute	-
结肠癌	药物发现	美国	Barbara Ann Karmanos Cancer Institute	2011-08-17
大肠恶性肿瘤	药物发现	美国	Barbara Ann Karmanos Cancer Institute	2011-08-17
复发性结肠癌	药物发现	美国	Barbara Ann Karmanos Cancer Institute	2011-08-17

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临床结果

适应症

分期

评价

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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


NCT01420874 \| NCT02620865 (Pubmed \| Oncoimmunology) 人工标引	临床1/2期	胰腺癌	7	anti-CD3 x anti-EGFR bispecific antibody	(遞範範衊夢糧鑰糧鬱憲) = 壓齋膚簾衊鑰鏇觸鬱簾觸醖艱鹽顧夢構獵願選 (簾觸衊製繭鑰網膚膚鹽 ) 更多	积极	2020-06-10
AACR2016	N/A	头颈部肿瘤	63	Cetuximab-based therapy + high ADCC + EGFR 3+ status	積願糧齋築願醖壓淵膚(衊網醖鹹鑰蓋鹽顧構製) = Median ADCC response at treatment start for all patients was 56.1% (range 5-99%) 淵選遞鬱範鹹淵繭築鏇 (膚夢糧壓壓襯衊壓遞齋 )	积极	2016-07-15
AACR2016	N/A	头颈部肿瘤	63	Cetuximab-based therapy + low ADCC + EGFR 3+ status		积极	2016-07-15
ASCO2012	临床1期	实体瘤 \| 复发性非小细胞肺癌	6	Anti-CD3 x anti-EGFR bispecific antibody (EGFRBi)	鏇構夢膚襯廠築鹽鹹艱(鑰憲簾醖鬱衊積願蓋製) = grade 2= 1 pt, grade 3= 1 pt 艱遞鏇顧網網願蓋網膚 (衊膚襯襯簾糧鹽淵艱餘 ) 更多	-	2012-05-20