TWI798243B - 治療癌症的方法 - Google Patents
治療癌症的方法 Download PDFInfo
- Publication number
- TWI798243B TWI798243B TW107126967A TW107126967A TWI798243B TW I798243 B TWI798243 B TW I798243B TW 107126967 A TW107126967 A TW 107126967A TW 107126967 A TW107126967 A TW 107126967A TW I798243 B TWI798243 B TW I798243B
- Authority
- TW
- Taiwan
- Prior art keywords
- agent
- cancer
- dose
- administered
- treating cancer
- Prior art date
Links
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C07K16/2803—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily
- C07K16/2818—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily against CD28 or CD152
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7052—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
- A61K31/706—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom
- A61K31/7064—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines
- A61K31/7068—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K33/00—Medicinal preparations containing inorganic active ingredients
- A61K33/24—Heavy metals; Compounds thereof
- A61K33/243—Platinum; Compounds thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
- A61K39/39533—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals
- A61K39/39541—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals against normal tissues, cells
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
- A61K39/39533—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals
- A61K39/3955—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals against proteinaceous materials, e.g. enzymes, hormones, lymphokines
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/22—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against growth factors ; against growth regulators
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
- A61K2039/507—Comprising a combination of two or more separate antibodies
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/545—Medicinal preparations containing antigens or antibodies characterised by the dose, timing or administration schedule
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Immunology (AREA)
- Organic Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Molecular Biology (AREA)
- Engineering & Computer Science (AREA)
- Biophysics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Genetics & Genomics (AREA)
- Biochemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Mycology (AREA)
- Microbiology (AREA)
- Inorganic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Endocrinology (AREA)
- Biomedical Technology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Steroid Compounds (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Abstract
揭露一種用於在一有需要之個體中治療癌症的方法,包含對該個體投予一抗PD-1藥劑,其與一種或多種抗癌藥劑組合投予,其中該抗PD-1藥劑與該一種或多種抗癌藥劑每一者係以單獨投予對治療癌症無效的量投予,以提供對治療癌症的不可預期的協同作用。
Description
本發明係關於一種用於治療癌症的方法。
以程序性細胞死亡 1(programmed cell death,PD-1)受體與其配體為標的的抗體已在包括泌尿上皮細胞癌(urothelial carcinoma,UC)等多種腫瘤中顯示其抗腫瘤能力。這些抗體對於器官移植患者的療效與安全性因為移植物排斥作用的風險而缺乏研究。
本發明提供一種用於在一有需要之個體中治療癌症的方法,包含對該個體投予一抗PD-1藥劑,其與一種或多種抗癌藥劑組合投予。
在本發明的部分具體實施例中,該抗PD-1藥劑為一抗PD-1抗體。在一具體實施例中,該抗PD-1抗體為吉舒達(pembrolizumab)。
在本發明的部分具體實施例中,該一種或多種抗癌藥劑包含癌思停(bevacizumab)、順鉑(cisplatin)與健擇(gemcitabine)。
根據本發明的部分具體實施例,該抗PD-1藥劑與該一種或多種抗癌藥劑每一者係以會產生治療癌症的協同作用之量投予。
在本發明的部分具體實施例中,該癌症為泌尿上皮細胞癌。
在本發明的部分具體實施例中,該個體為接受異體移植者。根據本發明的部分具體實施例,該抗PD-1藥劑與該一種或多種抗癌藥劑係以不會造成異體移植排斥作用的量投予。
應理解的是,前面的一般性描述與下面的詳細描述均僅為例示性及解釋性的,而不是對本發明的限制。
本發明提供一種用於在一有需要之個體中治療癌症的方法,包含對該個體投予一抗PD-1藥劑,其與一種或多種抗癌藥劑組合投予。
在本發明的部分具體實施例中,該抗PD-1藥劑為抗PD-1抗體。在一具體實施例中,該抗PD-1抗體為吉舒達。
在本發明的部分具體實施例中,該一種或多種抗癌藥劑包含癌思停、順鉑及健擇。
根據本發明的部分具體實施例,該抗PD-1藥劑與該一種或多種抗癌藥劑每一者係以會產生治療癌症的協同作用之量投予。
在本發明的部分具體實施例中,該癌症為泌尿上皮細胞癌。
在本發明的部分具體實施例中,該個體為接受異體移植者。根據本發明的部分具體實施例,該抗PD-1藥劑與該一種或多種抗癌藥劑係以不會造成異體移植排斥作用的量投予。
藉由以下實例進一步說明本發明,這些實例是為了說明而非限制的目的而提供。
實例
實例1:在不改變免疫抑制劑的劑量下,合併抗PD-1免疫療法可使腫瘤退行與保持移植體功能
一名患有末期腎臟病之61歲婦人於2008年四月進行死體腎臟移植。其患有糖尿病與高血壓等重大疾病。移植手術後其移植體在免疫抑制藥劑普賴蘇濃(prednisolone)、普樂可復(tacrolimus)與山喜多(mycophenolate mofetil)作用下維持穩定狀態。2009年六月中斷普賴蘇濃給藥。
她在2013年五月進行左側腎輸尿管切除與膀胱袖口切除後,被診斷出在左側輸尿管下三分之一處罹患UC。在2013年九月至2016年三月間,她因復發性膀胱癌接受了多次的經尿道膀胱腫瘤切除術,並自膀胱內灌注泛艾黴素(pharmarubicin)、排多癌注射劑(mitomycin C)與卡介苗(bacillus Calmette-Guerin)。2016年七月,她的病歷上記載排尿困難及陰道小量出血。正子電腦斷層造影與子宮頸活檢顯示復發性UC侵入移植的腎盂、膀胱、子宮頸及陰道(圖1
,(A))。
2016年八月她接受了靜脈注射一抗PD-1單株抗體(吉舒達[1 mg/kg] )與抗癌藥劑(癌思停[4 mg/kg]、順鉑[50 mg/m2
]及健擇[500 mg/m2
] )。4個療程後,於2016年十月的正子電腦斷層造影顯示了顯著的腫瘤退行(圖1
,(B))。2017年三月,正子電腦斷層造影證實11個療程後仍有持續性部分有效反應。在抗PD-1免疫療法治療後,以固定山喜多劑量(1 g/天),以及緩慢地自9 g/天增加至10 g/天,使血液中普樂可復濃度維持在5至10 ng/mL的治療下,移植體維持穩定的功能(圖1
,(C))。該婦人出現因免疫引起的斑性丘狀發疹,但在抗組織胺治療下可完全消除。
以免疫檢察點抑制劑對抗惡性細胞與表現外來抗原的細胞(如異體移植) 促使的免疫細胞活化,已知與細胞及抗體介導排斥作用有關[2,3]。現有文獻中,除了患有轉移性十二指腸腺癌的腎臟移植患者外,已廣泛地報導抗PD-1藥劑治療後引發異體移植排斥作用。在保疾伏(nivolumab)治療後逐漸減少康速龍錠(Prednisolone)劑量,以及以斥消靈錠(sirolimus)取代以普樂可復治療,可維持異種移植體的功能與使腫瘤退行[4]。本發明所載之患者,在不改變免疫抑制劑的劑量下,合併使用抗PD-1藥劑與抗癌藥劑可順利地維持異體移植體的功能與降低腫瘤負荷。近來研究結果顯示化學療法可透過消除免疫抑制細胞(例如骨髓來源抑制細胞或調節T細胞),與健擇或鉑類藥物一起使用達到增強抗癌療效[5]。此外,抗血管新生劑可以藉由使腫瘤新生血管正常化提升內源的免疫抗腫瘤反應[5]。因此,結合抗PD-1藥劑與抗癌藥劑可產生良好的療效且不會增加免疫引起的移植排斥作用。
本領域中的通常知識者將理解,可以對上述具體實施例進行改變而不脫離其廣泛的發明構思。因此,應當理解,本發明不限於所揭露的特定具體實施例,而是旨在涵蓋由所附的申請專利範圍所界定的本發明的精神及範圍內的修改。
參考文獻 1. Bellmunt J, de Wit R, Vaughn DJ et al. Pembrolizumab as Second-Line Therapy for Advanced Urothelial Carcinoma. N Engl J Med 2017; 376: 1015-1026. 2. Lipson EJ, Bagnasco SM, Moore J, Jr. et al. Tumor Regression and Allograft Rejection after Administration of Anti-PD-1. N Engl J Med 2016; 374: 896-898. 3. Boils CL, Aljadir DN, Cantafio AW. Use of the PD-1 Pathway Inhibitor Nivolumab in a Renal Transplant Patient With Malignancy. Am J Transplant 2016; 16: 2496-2497. 4. Barnett R, Barta VS, Jhaveri KD. Preserved Renal-Allograft Function and the PD-1 Pathway Inhibitor Nivolumab. N Engl J Med 2017; 376: 191-192. 5. Apetoh L, Ladoire S, Coukos G, Ghiringhelli F. Combining immunotherapy and anticancer agents: the right path to achieve cancer cure? Ann Oncol 2015; 26: 1813-1823.
當結合圖式閱讀時,將更佳地理解前述發明內容以及以下對本發明的詳細描述。為了說明本發明的目的,在圖式中顯示目前較佳的具體實施例。
圖式中:
圖1顯示治療前後的正子電腦斷層造影、隨時間的血清肌酸酐與普樂可復(tacrolimus;FK506)濃度以及尿蛋白/肌酸酐比值。 (A) 在治療開始前,移植的腎盂、膀胱、子宮頸及陰道出現代謝亢進。(B) 治療3個月後,代謝亢進顯著的消除。(C) 穩定的血清肌酸酐與普樂可復(FK506)濃度,以及尿蛋白/肌酸酐比值。
Claims (4)
- 一種抗PD-1藥劑在製備與抗癌藥劑組合投予以治療癌症之藥物之用途,其中該抗PD-1藥劑與所述抗癌藥劑每一者係以單獨投予對治療癌症無效的量對有需要的個體投予,以提供對治療癌症的不可預期的協同作用,其中該抗PD-1藥劑為吉舒達(pembrolizumab)且其劑量為1mg/kg;其中所述抗癌藥劑為癌思停(bevacizumab)、順鉑(cisplatin)及健擇(gemcitabine)之組合;且其中癌思停的劑量為約4mg/kg,順鉑的劑量為約50mg/m2,以及健擇的劑量為約500mg/m2。
- 如請求項1之用途,其中該癌症為泌尿上皮細胞癌(urothelial carcinoma)。
- 如請求項1之用途,其中該個體為接受異體移植者。
- 如請求項3之用途,其中該抗PD-1藥劑與所述抗癌藥劑係以不會造成異體移植排斥作用的量投予。
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US201762542432P | 2017-08-08 | 2017-08-08 | |
US62/542,432 | 2017-08-08 |
Publications (2)
Publication Number | Publication Date |
---|---|
TW201909915A TW201909915A (zh) | 2019-03-16 |
TWI798243B true TWI798243B (zh) | 2023-04-11 |
Family
ID=65274680
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
TW107126967A TWI798243B (zh) | 2017-08-08 | 2018-08-02 | 治療癌症的方法 |
Country Status (2)
Country | Link |
---|---|
US (1) | US10927175B2 (zh) |
TW (1) | TWI798243B (zh) |
Families Citing this family (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
TW202144409A (zh) * | 2020-05-12 | 2021-12-01 | 大陸商信達生物制藥(蘇州)有限公司 | 抗vegf抗體和抗pd-1抗體組合用於預防或治療疾病的應用 |
Family Cites Families (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP3760229A3 (en) * | 2014-05-15 | 2021-04-07 | Bristol-Myers Squibb Company | Treatment of lung cancer using a combination of an anti-pd-1 antibody and another anti-cancer agent |
-
2018
- 2018-08-02 US US16/053,234 patent/US10927175B2/en active Active
- 2018-08-02 TW TW107126967A patent/TWI798243B/zh active
Non-Patent Citations (1)
Title |
---|
網路文獻 Phase 2 Study of Pembrolizumab in Combination with Gemcitabine and Cisplatin as Neoadjuvant Therapy. https://clinicaltrials.gov/ct2/history/NCT02690558?V_1=View#StudyPageTop (2016/02/24) 2016/02/24 |
Also Published As
Publication number | Publication date |
---|---|
US10927175B2 (en) | 2021-02-23 |
TW201909915A (zh) | 2019-03-16 |
US20190048081A1 (en) | 2019-02-14 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN111065411B (zh) | Pd-1抗体和vegfr抑制剂联合治疗小细胞肺癌的用途 | |
WO2018068691A1 (zh) | 一种抗pd-1抗体和vegfr抑制剂联合在制备治疗癌症的药物中的用途 | |
WO2014142220A1 (ja) | 抗腫瘍剤 | |
CN102427728A (zh) | 用硫代秋水仙碱衍生物进行联合治疗 | |
WO2016204193A1 (ja) | 抗がん剤 | |
Al Jarroudi et al. | Anti-programmed cell death protein 1 (PD-1) immunotherapy for metastatic hepatocellular carcinoma after liver transplantation: a report of three cases | |
US20190307723A1 (en) | Compositions and methods for intravenous administration of 2-bromo-1-(3,3-dinitroazetidin-1-yl)ethanone | |
Iwase et al. | A phase II multi-center study of triple therapy with paclitaxel, S-1 and cisplatin in patients with advanced gastric cancer | |
JP7491220B2 (ja) | 免疫チェックポイント阻害薬およびfolfirinox療法との併用によるがん治療 | |
Lum et al. | Acute kidney allograft rejection precipitated by lenalidomide treatment for multiple myeloma | |
KR20230113594A (ko) | Pik3ca 돌연변이 암을 치료하기 위한 병용 요법 | |
KR101978108B1 (ko) | 암 세포의 대사 특이성에 기초하는 신규 항 악성 종양제 | |
LoRusso et al. | Icrucumab, a fully human monoclonal antibody against the vascular endothelial growth factor receptor-1, in the treatment of patients with advanced solid malignancies: a Phase 1 study | |
TWI798243B (zh) | 治療癌症的方法 | |
JP2019508433A (ja) | Liv1−adc及び化学療法剤を用いた併用療法 | |
Lee et al. | One‐Step Method for Instant Generation of Advanced Allogeneic NK Cells | |
TW202317183A (zh) | 藉由併用cd47抑制物質、免疫檢查點抑制物質及標準療法之癌症治療法 | |
US20230172882A1 (en) | Method For Treating Pancreatic Cancer | |
CN111166878B (zh) | 靶向肿瘤抗原的抗体与iNKT细胞的组合的制备方法与用途 | |
RU2580888C2 (ru) | Фармацевтическая композиция для лечения рака | |
EP3466422B1 (en) | Use of z-butylidenephthalide in activating autoimmune system | |
WO2012131487A2 (en) | Compositions and methods for the treatment of cancer | |
Tiersten et al. | Phase I/II study of tandem cycles of high-dose chemotherapy followed by autologous hematopoietic stem cell support in women with advanced ovarian cancer | |
JP6992984B2 (ja) | 腫瘍内静脈形成促進剤 | |
Heidari et al. | Interdisciplinary Approach in Hematological Cancers |