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대메뉴안내: Bio마켓
신제품 신기술 할인행사 시약벤더 제품평가 회원기업 벼룩시장 우수제품 인증제도 
 목록 조회142  인쇄  주소복사  소셜네트워크로 공유하기
[안티바디센터] Abnova CAR T Cell를 소개합니다.
제품(기술)분류 : 시약 > Antibody

전화 : 1670-5933

메일 : antibody(at).antibodycenter.co.kr

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Fighting Cancer using CAR T-cells

  • Effectiveness: 100% remission observed in non-Hodgkin lymphoma, chronic lymphocytic leukemia and, acute lymphoblastic leukemia
  • Pharmaceutical giants: Kite Pharma (KTE-C19), Novartis (CTL019) and Pfizer (UCART19) racing to received first FDA approval
  • Breakthrough: First “Off-the-shelf” allogenic CAR T product, UCART123 (Cellectis) received IND approval
  • Ongoing: 20+ active pipelines targeting 40+ cancers in 142 clinical trials1
  • Forecast: over 100% annual market growth rate, market worth USD 30 billion by 20302

Set Backs

  • Adverse effects: cytokine storm induction
  • Chronic inflammation after complete tumor remission
  • Halt: Juno Therapeutics announces a halt on its lead product JCAR015 after five deaths of cerebral edema in its phase II clinical trial

Safety Measures

  • Suicide genes introduction: trigger conditional apoptosis and prevent CARs from attacking healthy tissues3
  • Raising the bar and avoid off-targeting: engagement of two antigens simultaneously to induce effective immune response4,5
  • Inducible technology: control of T-cell potency, proliferation and persistence:
    • Inducible dimerization: GoCAR-T Technology (Bellicum)6
    • Ongoing: Tet-on CAR expression7
    • Forecast: CD19-CAR RUSH (Theravectys)8

 

Mechanistic Overview of CARs targeting cancer cells

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This figure has been adapted and altered from Kershaw et al., Nature Reviews Cancer, 2013

 

CARs are composed of four domains:

  • (1) Single chain antibody variable fragment (scFv) extracellular binding domain targeting specific tumor surface antigens
  • (2) Hinge domain
  • (3) Transmembrane domain
  • (4) Cytoplasmic signaling domain: trigger T cell proliferation, survival and cytokine production

First Generation

  • Containing only 1 single signaling domain derived from CD3ζ

Second Generation

  • Developed to contain a co-stimulatory domain, 2 signaling domains in total: represented here by CD28 and CD3ζ

Third and Fourth Generation

  • Incorporates additional co-stimulatory domains, 3 or 4 signaling domains in total: Image depicted a third generation CARs by CD28, CD137 and CD3ζ

 

References

1. ClinicalTrials.gov
2. RootsAnalysis Product Code: RA10047
3. Monica and Bondanza, 2011
4. Kloss et al., 2012
5. Wilkie et al., 2012
6. Bellicum Pharmaceuticals
7. Kiyoi et al., Cancer Immunol Res. 2016. doi: 10.1158/2326-6066

 

 

Key players in CARs induced dowmstream signaling pathways

 

NF-kB signaling pathway

AKT1

AKT2

CD14

CD28

CHUK

IKBKB

IL1A

IL1R1

IL1RAP

IRAK1

IRAK2

LBP

RELB

TRA

TLR4

TNF

TNFRSF1A

TNFRSF1B

TRAF2

TRAF6

UBA52

UBB

UBC

SUMO1

IKBKG

IKBKAP

TRADD

RIPK2

MAP3K14

AKT3

IRAK3

LY96

TRAJ18

TRAC

ECSIT

TOLLIP

 

Cytokines and Inflammatory Response

CD4

CSF1

CSF2

CSF3

CXCL1

CXCL2

HLA-DRA

HLA-DRB1

IFN1

IFNB1

IFNG

IL1A

IL1B

IL2

IL4

IL5

IL6

IL10

IL12B

IL13

IL15

PDGFA

TRA

TGFB1

TNF

 

NFAT in immune response

CALM1

CALM2

CALM3

CD3D

CD3E

CD3G

CD247

IKBKB

ITK

ITPR1

ITPR2

ITPR3

LCK

LCP2

NFATC2

NFKB1

NFKB2

NFKBIA

NFKBIB

NFKBIE

PLCG1

PPP3CA

PPP3CB

PPP3CC

PRKCQ

RAC1

REL

RELA

RELB

TRA

VAV1

ZAP70

LAT

TRAJ18

TRAC

 

 

 

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PRKCA monoclonal antibody(M01), clone 2F11

H00005578-M01

Immunofluorescence of monoclonal antibody to PRKCA on HeLa cell. [antibody concentration 10/ml]

 

 

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MAPK1 monoclonal antibody(M01), clone 1D1

H00005594-M01

Proximity Ligation Analysis of protein-protein interactions between MAPK3 and MAPK1. Huh7 cells were stained with anti-MAPK3 rabbit purified polyclonal 1:1200 and anti-MAPK1 mouse monoclonal antibody 1:50. Each red dot represents the detection of protein-protein interactioncomplex, and nuclei were counterstained with DAP1(blue)

 

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AKT1 monoclonal antibody(M04), clone 6D6

H00000207-M04

Immunoperoxidase of monoclonal antibody to AKT1 on formalin-fixed paraffin-embedded human colon. [antibody concentration 3/ml]

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