[Cell Signaling Technology] 항암제 발견을 위한 솔루션 (Solutions for Oncology Therapeutics Discovery)

CST-Solutions-for-Oncology-Therapeutics-Discovery

Cell Signaling Technology는 biology, application 등의 전문성을 바탕으로 oncology 치료 분야에서의 최신 연구와 새로운 치료 접근법에 발맞추어 새롭고 더 효과적인 치료법 개발로 이어질 수 있는 target에 대한 광범위한 항체 포트폴리오 및 서비스를 제공합니다. Oncology 신약 개발을 위한 다양한 연구 분야 및 과정에 따른 Cell Signaling Technology의 고품질 제품과 솔루션을 경험해 보세요.

신약 개발을 위한 Cell Signaling Technology의 맞춤형 서비스

서비스와 고객 맞춤 제안 개요
캐리어가 필요 없는 맞춤형 제형 (Carrier-free and Customized Formulations) 대량처리(High Throughput) ELISA 분석, 멀티플렉스 IHC, 유세포분석법 (Flow Cytometry) IHC 자동염색기기(Autostainers), 고성능 대량 스크리닝 및 분석(High Content Screening and Analysis) 등 모든 분석법과 플랫폼에 이상적입니다.
컨주게이션 항체 맞춤 제작 (Custom Antibody Conjugation) CST의 내부 전문가가 형광단(fluorophore), 비오틴, 효소 등 의뢰된 분석에 필요한 컨주게이션 항체를 직접 제작합니다.
프로테오믹스 분석 서비스 (Proteomics Analytical Services) CST 전문가 팀이 의뢰된 검체의 정량적 및 정성적 단백 프로파일 분석을 실시합니다. 프로테옴 (Proteome)을 규명하고 처치 전과 후의 번역 후 변형(Posttranslational Modifications)을 확인합니다.
벌크 배송과 로트 예약 (Bulk Quantities and Lot Reservation) CST가 파트너로 함께 하면 단일 로트 예약이나 대용량 주문이 가능하므로 잠재적 공급 문제가 없어집니다.
펩타이드 맞춤 제작과 관리 (Custom Peptides and Controls) CST는 고객의 기존 분석법에 필요한 관리 서비스를 제공합니다.

신약 개발 과정에 따른 Cell Signaling Technology의 맞춤형 솔루션

TARGET ID & VALIDATION SCREENING & LEAD OPTIMIZATION PRECLINICAL SAFETY & VALIDATION

TARGET ID AND MOA STUDIES

» Proteomic Services leveraging MS technology

IDENTIFY PRIMARY AND SECONDARY ENDPOINTS

» ELISA, HCS, Multiplex IHC

INDUSTRY-LEADING

IHC validation for biomarker identification and detection

TARGET VALIDATION

» Western Blot

» IHC and Multiplex IHC

» Flow Cytometry

PLATFORM COMPATIBILITY

» ELISA: MSD, AlphaLISA, HTRF, Quanterix

» Multiplex IHC: Akoya, Hyperion, Nanostring

» Automated WB  (e.g., ProteinSimple)

READY-TO-GO ELISA KITS

to key readouts and translational biomarkers

FLEXIBLE PACKAGING

» Trial Sizes

» Bulk Quantities

CUSTOM

» Matched antibody pairs (ELISA)

» Antibody conjugation services

IHC AUTOSTAINER COMPATIBLE

기존 플랫폼에서 작용하는 항체 - Cell Signaling Technology 항체는 여러 플랫폼과 기술에 널리 활용되고 있습니다.

PLATFORMS APPLICATION CONJUGATE TYPE* PRODUCT FORMAT

TR-FRET/LANCE/HTRF

AlphaLISA/Screen

MSD

Quanterix (Simoa)

Luminex

High Throughput ELISA

Fluorophores

Lanthanides

Biotin

Beads

BSA- and Azide-free Formulation

Matched Antibody Pairs

Optimized Concentration

CyTOF/Helios

Hyperion

MIBI

Flow Cytometry

Mass Cytometry/IMC

Multiplex IHC

Metal Ions

BSA- and Azide-free Formulation

Optimized Concentration

AKOYA (CODEX, OPAL)

ULTIVUE

IMMUNOSABER

NANOSTRING

Multiplex IHC Oligonucleotides Fluorophores
IHC Autostainers IHC N/A
ProteinSimple Automated WB N/A
High Content Screening & Analysis IF Imaging Fluorophores BSA- and Azide-free Formulation
* Some conjugates directly available for purchase from CST (other conjugate types may be proprietary)

항암제 개발

단백질 인산화효소는 세포주기 조절과 분화를 포함해 다양한 세포 기능에 관여합니다. Bcr/Abl이나 K-Ras와 같은 발암성 인산화효소에 대한 연구는 종양학을 발전시키고 항암치료 전략으로서 표적화 약물과 맞춤의학의 등장을 견인했습니다.

RTKs/Growth Factor Receptors

• EGFR, mutant EGFR
• ROS1, ALK
• Met
• VEGF Receptor
• PDGF Receptor

CST Solutions for Oncology Therapeutics Discovery-1

ROS1 (D4D6®) Rabbit mAb #3287: IHC analysis of paraffin-embedded human lung carcinoma using #3287.

Intracellular Kinases

• B-Raf
• Ras, K-Ras, Active Ras Detection Kit
• IRAK
• GSK3
• c-Jun

CST Solutions for Oncology Therapeutics Discovery-2

Ras (E8N8L) XP® Rabbit mAb #67648: IHC analysis of paraffin-embedded human non-small cell lung carcinoma using #67648.

Kinase Inhibition Readouts

• Phospho-Akt
• Phospho-p44/42 MAPK (Erk1/2)
• Phospho-p38 MAPK
• Phospho-MEK1/2
• Phospho-p70 S6 Kinase/p70 S6 Kinase

CST Solutions for Oncology Therapeutics Discovery-3

FastScan™ Phospho-p44/42 MAPK (Erk1/2) MAPK (Thr202/Tyr204) ELISA Kit #42173

세포주기 관문(checkpoint)과 DDR 경로는 협력하여 유전체(genome)를 보전합니다. 둘 중 하나라도 불안정하면 통제되지 않는 세포 증식과 돌연변이 축적으로 인해 종양 발생으로 이어질 수 있습니다. 이들 경로에서 결손을 표적화 함으로써 여러 암 유형에 대한 차세대 치료제를 개발할 수 있습니다.

Cell Cycle Regulation

• Phospho-Rb EGFR
• CDK4/6, CDK2
• Cyclin D1, Cyclin E1
• PLK1

CST Solutions for Oncology Therapeutics Discovery-4

FastScan™ Phospho-Rb (Ser807/811) ELISA Kit #10754

DNA Damage Response (DDR)

• Phospho-p53/p53, MDM2
• Phospho-Chk1/Chk1, Phospho-Chk2
• PARP, Rad51
• ATM, ATR

CST Solutions for Oncology Therapeutics Discovery-5

Phospho-Chk1 (Ser345) (133D3) Rabbit mAb #2348: Confocal IF analysis of C2C12 cells, untreated (left) or UV-treated (right), using #2348 (green). Actin filaments have been labeled with
DY-554 phalloidin (red).

Senescence

• p16 INK4A
• p21 Waf1/Cip1
• Lamin B1
• β-galactosidase Assays

CST Solutions for Oncology Therapeutics Discovery-6

p21 Waf1/Cip1 (12D1) Rabbit mAb #2947: IHC analysis of paraffin-embedded human breast carcinoma using #2947 in the presence of control peptide.

암세포 대사의 특징을 기술하는 것으로 시작된 암 대사 연구는 암세포가 대사학적으로 어떻게 재프로그래밍되어 이동, 침범, 전이에 영향을 미치는지를 이해하는 수준까지 발전했습니다. 대사경로를 표적화 하는 항암치료제는 암 성장을 억제하고 여러 가지 병용요법을 선택할 수 있게 해줍니다.

Glucose Metabolism

• Phospho-PKM2/PKM2
• Phospho-IGF-I Receptor/IGF-I Receptor
• Phospho-Insulin Receptor β/Insulin Receptor β
• Phospho-GSK-3β/GSK-3β
• Glut1

CST Solutions for Oncology Therapeutics Discovery-7

PKM2 (D78A4) XP® Rabbit mAb #4053: IHC analysis of paraffin-embedded human lung carcinoma using #4053.

Autophagy

• LC3B
• Phospho-mTOR/mTOR
• Atg13
• ULK1
• SQSTM1/p62

CST Solutions for Oncology Therapeutics Discovery-8

LC3B (E5Q2K) Mouse mAb #83506: Confocal IF analysis of HCT 116 cells treated with Chloroquine #14774 (50 μM, overnight) using #83506 (green). Actin filaments were labeled with β-Actin (13E5) Rabbit mAb #4970 (red) and nuclei were labeled with DAPI #4083 (blue).

Fatty Acid and Amino Acid Metabolism

• Phospho-Acetyl-CoA Carboxylase/
Acetyl-CoA Carboxylase
• Perilipin-1
• Arginase-1
• ASS1
• Phospho-BCKDH

CST Solutions for Oncology Therapeutics Discovery-9

Phospho-Acetyl-CoA Carboxylase (Ser79) (D7D11) Rabbit mAb #11818: IHC analysis of paraffin-embedded human breast carcinoma using #11818.

상피-중간엽 전이(EMT)는 암이 악성으로 진행되는 데에 핵심적 역할을 해서 전이와 치료 내성 발생을 촉진한다고 알려진 세포 내 프로그램입니다. EMT 활성화를 표적으로 한 새로운 항암제는 암이 전신으로 전이되는 것을 억제하고 치료 경과를 개선할 수 있습니다.

Transcription Factors/Co-activators

• Phospho-STAT3 ELISA
• c-Myc
• GLI
• p65
• PAX5

CST Solutions for Oncology Therapeutics Discovery-10

PathScan® Phospho-Stat3 (Tyr705) Sandwich ELISA Kit #7300

Signaling Pathways

• Phospho-SMAD2/3 ELISA, TGF-β
• Wnt/β-Catenin
• YAP/TAZ, LATS1
• DLL3, Notch1/2/3

CST Solutions for Oncology Therapeutics Discovery-11

FastScan™ Phospho-Smad2 (Ser465/467) ELISA
Kit #86932

Key Biomarkers

• Vimentin
• E-Cadherin
• Vinculin
• Fibronectin
• α-Smooth Muscle Actin

CST Solutions for Oncology Therapeutics Discovery-12

Vimentin (D21H3) XP® Rabbit mAb #5741: IHC analysis of paraffin-embedded human breast carcinoma using #5741.

세포사멸 회피는 암의 대표적 성질입니다. 암세포의 사멸을 촉발시키는 세포사멸 경로를 표적화 하는 것은 한 가지 암 유형에 국한하지 않고 널리 활용가능한 항암제의 개발을 기대할 만한 유망한 전략입니다.

Intrinsic Pathway

• Bcl-2, Bcl-xL, Mcl-1
• Bax, Bim, Bad
• Puma, Noxa

CST Solutions for Oncology Therapeutics Discovery-13

Bcl-xL (54H6) Rabbit mAb #2764: IHC analysis of paraffin-embedded human lung carcinoma, using #2764.

Extrinsic Pathway

• TRAIL, DR4, DR5
• TNF, TNF-R1, TNF-R2
• FasL, Fas

CST Solutions for Oncology Therapeutics Discovery-14

DR5 (D4E9) XP® Rabbit mAb #8074: Confocal IF analysis of HT-1080 cells using #8074 (green). Blue pseudocolor = DRAQ5® #4084 (fluorescent DNA dye).

Caspase Activators

• Smac/Diablo
• XIAP, c-IAP1, c-IAP2
• Survivin, Livin

CST Solutions for Oncology Therapeutics Discovery-15

Survivin (71G4B7) Rabbit mAb #2808: IHC analysis of paraffin-embedded human transitional epithelial carcinoma of the bladder using #2808.

비정상 후성유전학적 반응과 유전자 돌연변이 모두 종양생성에 기여하지만, 현재 대부분의 항암제는 유전자 이상에 표적화 하는 것에 집중하고 있습니다. 신생 세포를 정상세포와 비슷하게 행동하도록 재프로그래밍하는 후성유전학적 약물은 기존 치료 전략의 대안이 될 수 있으며 다른 항암제와의 복합요법으로서 가장 큰 효과를 발휘할 것으로 기대됩니다.

Methylation and Demethylation Inhibitors

• Histones Regulators: Ezh2, LSD1, H3K27me3
• DNA Regulators: DNMTs, TETs, 5- ethylcytosine (5-mC), 5-Hydroxymethylcytosine (5-hmC)
• RNA Regulators: N6-Methyladenosine (m6A),
METTL3, FTO

CST Solutions for Oncology Therapeutics Discovery-16

Ezh2 (D2C9) XP® Rabbit mAb #5246: IHC analysis of paraffin-embedded human lymphoma using #5246.

Acetylation and Deacetylation Inhibitor

 

• Histones Regulators: CBP, p300, H3K27ac, HDACs

 

CST Solutions for Oncology Therapeutics Discovery-17

p300 (D8Z4E) Rabbit mAb #86377: IHC analysis of paraffin-embedded human squamous cell lung carcinoma using #86377.

Histone Mutations

 

• Histones: H3K27M, H3K36M, H3K9M,
H3K27me3, H3K36me3, H3K9me3

 

CST Solutions for Oncology Therapeutics Discovery-18

Histone H3 (K9M Mutant Specific) (E4N7V) Rabbit mAb #54905: IHC analysis of paraffin-embedded histone H3 K9M mutant mouse small intestine using #54905. (Tissue courtesy of Dr. Aaron Huebner, Hochedlinger Lab at Massachusetts General Hospital, Boston, MA.)

면역항암제 개발

종양의 성장과 생존은 악성세포 뿐만 아니라 종양미세환경(TME)을 구성하는 내피세포, 기질 섬유아세포, 면역세포로부터의 신호에 의해 좌우됩니다. 내피세포 및 섬유아세포와의 복잡한 상호작용 뿐만 아니라 세포독성 T 세포에 의한 종양 침투 정도를 바탕으로 임상적 경과를 예측하고 조정할 수 있습니다.

Immune Cell Infiltration

• CD3
• CD8α
• CD68
• CD19
• CD11c

CST Solutions for Oncology Therapeutics Discovery-19

CD8α (D8A8Y) Rabbit mAb #85336: IHC analysis of paraffin-embedded human Crohn’s diseased colon using #85336.

Immune Cell Function

• FoxP3
• HLA-DR
• CD86
• IL-1β
• IL-8

CST Solutions for Oncology Therapeutics Discovery-20

CD86 (E2G8P) Rabbit mAb #91882: IHC analysis of paraffin-embedded human lung  denocarcinoma using #91882 performed on the Leica BOND Rx.

Therapeutic Targets

• CD47
• CD73
• SIRPα
• CSF-1

CST Solutions for Oncology Therapeutics Discovery-21

CD47 (D3O7P) Rabbit mAb #63000: IHC analysis of paraffin-embedded human urothelial carcinoma using #63000 performed on the Leica BOND Rx.

Multiplex IHC Compatibility

Gold-Standard IHC Validation Enables Multiplex Discovery

 

CST Solutions for Oncology Therapeutics Discovery-22

 

Multiplex IHC analysis of paraffin-embedded malignant melanoma on the CODEX platform using Granzyme B (D6E9W) Rabbit mAb #46890, shows the widespread labeling of infiltrating immune cells in this sample, along with other markers.

Proteomic and Genomic Correlation using Nanostring Technology

Reliably Correlate Protein Expression with Genomic Data and IHC

CST Solutions for Oncology Therapeutics Discovery-23

Serial sections of each NSCLC specimen were stained with antibodies for each of the noted proteins. Tumor Ras G12C genotype of each sample (A–C) obtained from SNV analysis is indicated (+/-) on the left. An additional single serial section was simultaneously stained with DNA-barcoded antibodies. Normalized digital counts from
the nCounter analysis for each protein are shown from left to right, colorcoded to each
sample (A–C).

PD-1, PD-L1, CTLA-4와 같은 면역관문을 차단하는 T 세포-표적성 면역조절제는 항암치료의 접근 방식에 혁신을 초래했습니다. 이 치료법은 후기 병기의 일부 환자에서 유의미하게 경과를 개선하고 있습니다.

Checkpoint Therapy Targets

• PD-1
• PD-L1
• TIGIT
• B7-H3
• ICOS

CST Solutions for Oncology Therapeutics Discovery-24

TIGIT (E5Y1W) XP® Rabbit mAb #99567: IHC analysis of paraffin-embedded human non-small cell lung carcinoma using #99567.

T Cell Exhaustion

• PD-1
• TOX
• TCF1
• TIM-3
• LAG3

CST Solutions for Oncology Therapeutics Discovery-25

Tox/Tox2 (E6I3Q) Rabbit mAb #73758: IHC analysis of paraffin-embedded human colon carcinoma using #73758 performed on the Leica® BOND™ Rx.

T Cell Activity

• IFN-γ
• TNF-α
• Granzyme B
• Cytotoxicity Assay
• Proliferation Assay

CST Solutions for Oncology Therapeutics Discovery-26

IFN-γ (D3H2) XP® Rabbit mAb (Alexa Fluor® 488 Conjugate) #12942: Flow cytometric analysis of human peripheral blood mononuclear cells treated with TPA, Ionomycin and Brefeldin
A using #12942. Co-stained with CD3 (UCHT1) Mouse mAb (APC Conjugate) #19881.

선천적 면역계를 활성화하면 암세포가 촉발하는 면역 회피 경로를 막을 수 있습니다. 이 기전을 심층 이해한다면 다른 치료 전략과 병용하여 장기적으로 임상적 혜택을 유도할 새로운 면역항암제를 개발할 수 있습니다.

Inflammasome

• NLRP3
• Caspase-1/Cleaved Caspase-1
• IL-1β/Cleaved IL-1β
• ASC/TMS1
• IL-18

CST Solutions for Oncology Therapeutics Discovery-27

IL-1β (3A6) Mouse mAb #12242: IHC analysis of paraffin-embedded human large intestine (ulcerative chronic colitis of the rectum) using #12242.

STING

• cGAS
• Phospho-STING/STING
• Phospho-TBK1/TBK1
• Phospho-IRF-3/IRF-3

CST Solutions for Oncology Therapeutics Discovery-28

Phospho-STING (Ser366) (E9A9K) Rabbit mAb #50907: Flow cytometric analysis of TPA differentiated THP-1 cells that have been activated to phosphorylate STING (green line) vs unactivated (blue). Isotype controls are shown by dashed lines.

TLR

• Phospho-IκBα/IκBα
• Phospho-IKKα/β/IKKα/β
• Phospho-p65/p65
• Phospho-TBK1/TBK1
• Phospho-IRF-3/IRF-3

CST Solutions for Oncology Therapeutics Discovery-29

NF-κB p65 (D14E12) XP® Rabbit mAb #8242: IHC analysis of paraffin-embedded human chronic cholecystitis using #8242.

면역세포 활성화 측정을 통해 새로운 면역항암제의 유효성 결정을 위한 선천적 면역계와 후천성 면역계의 활성화 정도를 평가할 수 있습니다.

T Cell Signaling

• Phospho-SLP-76 (Ser376)
• Phospho-NF-kB (Ser536)
• HPK1
• Phospho-Zap-70 (Tyr319)
• Phospho-Erk (Thr202/Tyr204)
• Phospho-SHP-2 (Tyr580)

CST Solutions for Oncology Therapeutics Discovery-30

PathScan® Phospho-SLP-76 (Ser376) Sandwich
ELISA Kit #78222

B Cell Signaling

• Phospho-Syk (Tyr525/526)
• Phospho-Btk (Tyr223)
• Phospho-Src Family (Tyr416)
• Phospho-CD79A (Tyr182)
• Phospho-SHP-1 (Tyr564)

CST Solutions for Oncology Therapeutics Discovery-31

PathScan® Phospho-Btk (Tyr223) Sandwich ELISA Kit #23843

Cytokine Response

• Phospho-STAT3 (Tyr705)
• Phospho-STAT5 (Tyr694)
• Phospho-STAT6 (Tyr641)
• Phospho-STAT1 (Tyr701)
• Phospho-Jak2 (Tyr1007/1008)
• Phospho-Jak1 (Tyr1034/1035)

CST Solutions for Oncology Therapeutics Discovery-32

FastScan™ Phospho-Stat1 (Tyr701) ELISA Kit #40716

적응세포치료법과 세포 생존력 분석

적응세포치료법은 종양침투성 림프구를 활용하거나 새로운 T 세포 수용체(TCR)나 키메라 항원 수용체(CAR)를 발현하도록 유전자 조작된 T 세포를 활용해 종양세포를 박멸하는 면역치료 전략입니다. 이 치료전략은 항-종양 효과 개선, 독성 감소, 동종세포(allogenic) 이용가능성 파악을 목표로 하여 개발되고 있습니다.

Monitoring CAR-T Target Expression

• TNFRSF17/BCMA
• CD19
• IL-13RA2
• CD20
• CD22

CST Solutions for Oncology Therapeutics Discovery-33

TNFRSF17/BCMA (E6D7B) Rabbit mAb #88183: IHC analysis of paraffin-embedded human normal colon using #88183.

T Cell Phenotyping

• CD4
• CD8
• PD-1
• LAG3
• TIM-3

CST Solutions for Oncology Therapeutics Discovery-34

TIM-3 (D5D5R™) XP® Rabbit mAb (Alexa Fluor® 488 Conjugate) #54669: Flow cytometric analysis of primary CD4+ T cells (green, positive) and Jurkat cells (blue, negative).

T Cell Functional Analysis

• Cytotoxicity assay
• Proliferation assay
• Granzyme B
• IFN-γ
• TNF-α

CST Solutions for Oncology Therapeutics Discovery-35

Cell Proliferation Tracer Kit (Fluorometric, Violet 450) #48444: Live human peripheral blood mononuclear cells were labeled with the kit comparing treatment to induce cellular division (green) vs. untreated (solid blue line). Unstained cells were used as a control (dashed line). Multiple peaks equate to multiple rounds
of cellular division (proliferation) following treatment.

세포 생존력이란 검체 중 건강한 세포의 백분율을 의미합니다. 세포 생존력의 생물학적 측정치를 이용하여 암세포의 증식을 억제하거나 세포사멸을 촉진하도록 개발된 치료제의 안전성과 유효성을 평가합니다.

Proliferation

• Ki-67
• PCNA
• Phospho-Histone H3
• BrdU Proliferation Assay

 

CST Solutions for Oncology Therapeutics Discovery-36

 

Ki-67 (8D5) Mouse mAb #9449: IHC analysis of paraffin-embedded human breast carcinoma using #9449.

Cell Death

• Apoptosis: Cleaved Caspase-3 ELISA, Cleaved
PARP ELISA, Annexin V Assay, Mitochondrial
Membrane Potential Assay
•  Necroptosis: RIP/Phospho-RIP ELISA,
Phospho-MLKL
• Pyroptosis: NLRP3, Cleaved Gasdermin,
Cleaved Caspase-1

CST Solutions for Oncology Therapeutics Discovery-37

PathScan® Phospho-RIP (Ser166) Chemiluminescent Sandwich ELISA Kit #88918

Viability

• XTT Cell Viability Assay
• Resazurin Cell Viability Assay

CST Solutions for Oncology Therapeutics Discovery-38

XTT Cell Viability Kit #9095: C2C12 cells were seeded at varying density in a 96-well plate and incubated overnight. The XTT assay solution was added to the plate and cells were incubated. The absorbance at 450 nm was measured at 1.0, 2.0, 3.0, 4.0, and 5.0 hours.

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