Recombinant Interleukin-15(National Cancer Institute)(Recombinant Interleukin-15(National Cancer Institute)) - 药物靶点：IL-15Rα_在研适应症：转移性实体瘤，复发癌，难治性癌症_专利_临床

概要

基本信息

药物类型

白细胞介素

别名

Recombinant Human IL15、rhIL15

靶点

IL-15Rα

作用方式

激动剂

作用机制

IL-15Rα激动剂(白细胞介素-15受体α亚基激动剂)

治疗领域

肿瘤

在研适应症

转移性实体瘤复发癌难治性癌症

非在研适应症

晚期恶性实体瘤皮肤黑色素瘤转移性非小细胞肺癌+ [7]

原研机构

National Cancer Institute

在研机构

National Cancer Institute

非在研机构-

权益机构-

最高研发阶段临床1期

首次获批日期-

最高研发阶段(中国)-

特殊审评-

登录后查看时间轴

关联

2

项与 Recombinant Interleukin-15(National Cancer Institute) 相关的临床试验

NCT03388632

/ Completed临床1期IIT

Phase I Study of Recombinant Interleukin 15 in Combination With Checkpoint Inhibitors Nivolumab and Ipilimumab in Subjects With Refractory Cancers

Background:
The drug Interleukin-15 (IL-15) activates the immune system. The drugs nivolumab and ipilimumab unblock immune cells. The drugs together may allow immune cells to recognize and attack cancer cells, causing tumors to shrink.
Objective:
To test the effects and maximum dose of IL-15, nivolumab, and ipilimumab.
Eligibility:
People ages 18 and older who have cancer that does not respond to treatment
Design:
Participants will be screened with:
* Medical history
* Physical exam
* Heart, blood, and urine tests
* Scans
Tumor biopsy: A small needle removes a tumor sample.
Participants will be in 1 of 3 treatment groups:
* IL-15 with nivolumab
* IL-15 with ipilimumab
* IL-15 with nivolumab and ipilimumab
Participants will take the drugs in four 6-week cycles. IL-15 is injected under the skin. The other two drugs are injected into an arm vein over 60-90 minutes. Participants may need to stay at the hospital 2-3 hours after the first dose of any drug to watch for side effects.
Each cycle will include:
* Weekly blood and urine tests
* 16 IL-15 injections
* 1 ipilimumab injection if applicable
* 3 nivolumab injections if applicable
* Blood tests weekly during cycles 1 and 2
* Urine tests weekly during cycles 1 and 2
* Scans and a tumor biopsy on day 42
After cycle 4, participants will stop taking IL-15. They will continue the other drugs until they can no longer tolerate the side effects, or their cancer gets worse. Those cycles will include:
* 1 ipilimumab injection if applicable
* 3 nivolumab injections if applicable
* Scans every other cycle
After participants stop treatment, their doctor will monitor their side effects for 4 months or until they go away.

开始日期2018-02-05

申办/合作机构

National Cancer Institute

NCT01727076

/ Completed临床1期IIT

A Phase 1 Study of Recombinant Human IL15 (rhIL15) in Adults With Advanced Solid Tumors: Melanoma, Renal Cell, Non-Small Cell Lung and Squamous Cell Head and Neck Cancer

This phase I trial studies the side effects and best dose of recombinant interleukin-15 in treating patients with melanoma, kidney cancer, non-small cell lung cancer, or head and neck cancer that has spread to other places in the body and usually cannot be cured or controlled with treatment. Recombinant interleukin-(IL)15 is a biological product, a protein, made naturally in the body and when made in the laboratory may help stimulate the immune system in different ways and stop tumor cells from growing.

开始日期2013-02-15

申办/合作机构

National Cancer Institute

100 项与 Recombinant Interleukin-15(National Cancer Institute) 相关的临床结果

登录后查看更多信息

100 项与 Recombinant Interleukin-15(National Cancer Institute) 相关的转化医学

登录后查看更多信息

100 项与 Recombinant Interleukin-15(National Cancer Institute) 相关的专利（医药）

登录后查看更多信息

59

项与 Recombinant Interleukin-15(National Cancer Institute) 相关的文献（医药）

2025-12-01·CYTOKINE

Characterizing the mechanisms underpinning interleukin-15Rα-mediated protection against sepsis and candidiasis

Article

作者: Tang, Yin ; Liu, Yuhan ; Xu, Banglao ; Yang, Jin ; Liu, Jiayu ; Li, Xin ; Yu, Renlin ; Zhao, Ping ; Tang, Ling ; Li, Sen ; Cao, Ju ; Liu, Yao ; Ding, Hao ; Tan, Wang ; Li, Jin

The interleukin (IL)-15Rα receptor has crucial, protective roles in sepsis and candidiasis via binding to its ligand, IL-15. However, the underlying mechanisms remain largely unexplored. In our study, we first confirmed the protective effects of IL-15 using clinical samples from patients with sepsis and candidiasis, and also in animal models with those conditions. We therapeutically administered IL-15 to IL-15Rα-deficient mice to elucidate the roles of IL-15Rα in sepsis and candidiasis treatment. Bacterial and fungal infections expedite mortality, caused organ damage, elevated the microbial burden in organs, and impaired macrophage recruitment, and subsequent microbial killing capacity. Notably, these adverse effects were alleviated via recombinant IL-15 supplementation, but this did not improve compromised conditions in IL-15Rα-deficient mice with sepsis. We show that IL-15Rα is required for protection against both bacterial and fungal sepsis, suggesting that this receptor could become a potential target for treating clinical sepsis and may hold significant clinical therapeutic value.

2025-12-01·Journal for ImmunoTherapy of Cancer

Phase 1 study evaluating the safety, preliminary efficacy, and pharmacodynamics of recombinant interleukin-15 in combination with nivolumab and ipilimumab in patients with refractory cancers

Article

作者: Augustine, Brooke ; Parchment, Ralph E ; Rubinstein, Larry V ; Mukherjee, Jessica ; Doroshow, James H ; Ahmed, Jibran ; Streicher, Howard ; Ferry-Galow, Katherine V ; Ma, Ning ; Bruns, Ashley ; Fung, King Leung ; Takebe, Naoko ; Shin, Sarah J ; Chen, Alice P ; O’Sullivan Coyne, Geraldine ; Fino, Kristin ; Johnson, Barry C

Purpose:

Combinations of immune checkpoint inhibitors and cytokine therapies have shown promise in cancer immunotherapy. We aimed to evaluate the safety, tolerability, and preliminary efficacy of recombinant human interleukin-15 (rhIL-15) in combination with nivolumab and ipilimumab in patients with advanced, refractory cancers.

Methods:

This open-label, non-randomized study employed a 3+3 dose-escalation design to determine the maximum tolerated dose (MTD) of rhIL-15 combined with fixed doses of nivolumab and ipilimumab. Safety and tolerability were assessed according to Common Terminology Criteria for Adverse Events (CTCAE) criteria, and preliminary efficacy was assessed according to Response Evaluation Criteria in Solid Tumors (RECIST) and immune-related RECIST (iRECIST) criteria. Pharmacodynamic studies evaluated changes in immune cell populations in peripheral blood and paired baseline and on-treatment tumor biopsies.

Results:

Thirty-one patients were enrolled, with a median age of 56 years (range: 24–81 years). Five patients received rhIL-15 with either nivolumab or ipilimumab in safety run-in cohorts, 26 patients received rhIL-15 with nivolumab plus ipilimumab. The most common cancer types were gastrointestinal (n=7) or gynecologic (n=5). The MTD was 1 µg/kg/day rhIL-15, 240 mg nivolumab, and 1 mg/kg ipilimumab. The triplet combination showed a manageable safety profile; the most common treatment-related adverse events (trAEs) were chills (20/26, 77%), fever (18/26, 69%), injection site reaction (15/26, 58%), anemia (14/26, 54%), and fatigue (14/26, 54%). Lymphopenia (4/26, 15%) was the most common grade 3/4 trAE. Pharmacodynamic analysis of tumor biopsies revealed increases in CD8+, CD8+CD3ζpY142+ (ie, activated CD8+T cells), PD-1+CD3+, and CD45RO+CD3+ (ie, memory T cells) in some patients. Tumor infiltration of natural killer (NK) and γδ T cells was also observed. NK cell populations in peripheral blood were modulated by rhIL-15. 11 of 26 patients (42%) had stable disease as a best response on the triplet regimen. A partial response was measured after cycle 1 in one patient (4%) with cholangiocarcinoma and confirmed after cycle 2; this patient completed 16 cycles.

Conclusions:

The combination of rhIL-15 with nivolumab and ipilimumab was safe and induced changes in immune cell populations in some patients. However, preliminary signs of efficacy were limited. Pharmacodynamic findings may support further clinical development of this combination with alternative dosing regimens or combinations of rhIL-15 with other therapeutic modalities.

2025-07-01·Journal for ImmunoTherapy of Cancer

Constitutive IL-7 signaling promotes CAR-NK cell survival in the solid tumor microenvironment but impairs tumor control

Article

作者: Dysthe, Matthew ; Baumgartner, Corrine ; Navin, Ishwar ; Pineda, Josue ; Parihar, Robin ; Rooney, Cliona M ; van Leeuwen, Dayenne

Background:

Adoptive transfer of chimeric antigen receptor (CAR)-expressing natural killer (NK) cells has demonstrated success against hematological malignancies. Efficacy against solid tumors has been limited by poor NK cell survival and function in the suppressive tumor microenvironment (TME). To enhance efficacy against solid tumors, stimulatory cytokines have been incorporated into CAR-NK cell therapeutic approaches. However, current cytokine strategies have limitations, including systemic toxicities, exogenous dependencies, and unwanted TME bystander effects. Here, we aimed to overcome these limitations by modifying CAR-NK cells to express a constitutively active interleukin (IL)-7 receptor, termed C7R, capable of providing intrinsic CAR-NK cell activation that does not rely on or produce exogenous signals nor activate bystander cells.

Methods:

We examined persistence, antitumor function, and transcriptional profiles of CAR-NK cells coexpressing C7R in a novel tumor immune microenvironment (TiME) co-culture system and against hematologic and solid tumor xenografts in vivo.

Results:

Peripheral blood NK cells expressing a CAR directed against the solid tumor antigen GD2 and modified with C7R demonstrated enhanced tumor killing and persistence in vitro compared with CAR-NK cells without cytokine support and similar functions to CAR-NK cells supplemented with recombinant IL-15. C7R.CAR-NK cells exhibited enhanced survival and proliferation within neuroblastoma TiME xenografts in vivo but produced poor long-term tumor control compared with CAR-NK cells supplemented with IL-15. Similar results were seen using C7R-expressing CD19.CAR-NK cells against CD19+leukemia xenografts. Gene expression analysis revealed that chronic signaling via C7R induced a transcriptional signature consistent with intratumor stressed NK cells with blunted effector function. We identified gene candidates associated with chronic cytokine-stressed NK cells that could be targeted to reduce CAR-NK cell stress within the solid TME.

Conclusion:

C7R promoted CAR-NK cell survival in hostile TMEs independent of exogenous signals but resulted in poor antitumor function in vivo. Our data reveals the detrimental role of continuous IL-7 signaling in CAR-NK cells and provides insights into proper application of cytokine signals when attempting to enhance CAR-NK cell antitumor activity.

100 项与 Recombinant Interleukin-15(National Cancer Institute) 相关的药物交易

登录后查看更多信息

研发状态

10 条进展最快的记录,

登录

后查看更多信息

适应症	最高研发状态	国家/地区	公司	日期
转移性实体瘤	临床1期	美国	National Cancer Institute	2018-02-05
复发癌	临床1期	美国	National Cancer Institute	2018-02-05
难治性癌症	临床1期	美国	National Cancer Institute	2018-02-05
晚期恶性实体瘤	临床1期	美国	National Cancer Institute	2013-02-15
皮肤黑色素瘤	临床1期	美国	National Cancer Institute	2013-02-15
转移性非小细胞肺癌	临床1期	美国	National Cancer Institute	2013-02-15
非小细胞肺癌IIIA期	临床1期	美国	National Cancer Institute	2013-02-15
非小细胞肺癌IIIB期	临床1期	美国	National Cancer Institute	2013-02-15
复发性头颈癌	临床1期	美国	National Cancer Institute	2013-02-15
复发性非小细胞肺癌	临床1期	美国	National Cancer Institute	2013-02-15

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


NCT03388632 (Phase 1 study, CTgov)	临床1期	转移性实体瘤 \| 难治性癌症 \| 复发癌	31	ipilimumab+nivolumab+rh IL-15 (All Participants in Escalation Phase of Arm C)	網壓糧艱選鬱鏇艱鬱醖 = 壓製遞窪積蓋膚鹽鏇鑰壓繭鬱廠憲網鹹襯糧願 (膚襯糧範鏇糧顧醖築糧, 鏇積襯夢糧衊壓憲獵窪 ~ 鬱製鑰鏇壓積積構蓋艱)	-	2025-12-03
				Recombinant Human Interleukin (rH IL-15)+Nivolumab (Arm A Doublet A - Recombinant Human Interleukin (rH IL-15) 0.5mcg/kg & Nivolumab 240mg)	醖壓廠糧鏇齋襯範鑰淵 = 壓淵積鬱憲簾鏇積餘廠襯鏇鹽窪夢廠膚醖願觸 (淵餘繭構願獵繭觸鏇膚, 糧選積網獵蓋餘顧蓋襯 ~ 繭鹽艱鬱膚廠糧鹹鹽膚) 更多
NCT01727076 (CITN11-02, SITC2015)	临床1期	复发性头颈癌 \| 非小细胞肺癌IIIA期 \| 皮肤黑色素瘤 ... 更多	18	rhIL-15 0.25 mcg/kg	窪築壓蓋範廠繭襯網衊(醖糧遞憲艱蓋簾製糧襯) = One of 3 patients treated with 3.0 mcg/kg rhIL-15 experienced a DLT; this cohort will be expanded. Higher doses of rhIL-15 were associated with profound increases in circulating NK cells with smaller but still significant increases in CD8+ T cells. Outpatient use of subcutaneous rhIL-15 is safe and will likely emerge as a key agent for combination with other cancer immunotherapies. 鑰夢醖蓋遞鏇顧製鏇鬱 (糧鏇製繭簾餘獵構遞壓 ) 更多	积极	2015-11-04
				rhIL-15 0.5 mcg/kg
NCT01727076 (CITN11-02, SITC2014)	临床1期	复发性头颈癌 \| 非小细胞肺癌IIIA期 \| 皮肤黑色素瘤 ... 更多	12	rhIL15 0.25 mcg/kg/dose	構膚壓餘襯膚築醖糧繭(鏇範壓廠選顧築膚窪淵) = grade 2 pancreatitis was observed in a metastatic melanoma patient and began 3 days after completing Cycle 1 treatment at 2.0 mcg/kg 鏇範繭願淵積艱廠範壓 (窪蓋衊鑰膚衊衊鹽網夢 )	积极	2014-11-06
				rhIL15 0.5 mcg/kg/dose