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● PBMC免疫系统人源化异种移植瘤模型(100个) ▶

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PBMC humanized CDX/PDX: 100

Note: ort, orthotopic transplantation of tumor fragments.

 

 

INTRODUCTION

 

PD-1/PD-L1 checkpoint inhibitors remain the most efficacious immuno-oncology (I-O) therapeutics, and their combinations with targeted therapies or other agents will lead to significant breakthroughs in cancer treatment. In addition, more and more new immunotherapy treatment modalities, such as the use of other checkpoint inhibitors, cytokines, and chimeric antigen receptors, are being developed at an increasingly rapid pace.

Assessment and development of I-O therapies require appropriate animal models in the context of both human immunity and human cancers. Yicon has successfully established a number of human PBMC-humanized xenograft models known as PBMCCDX/PBMCPDX for in vivo immunotherapy evaluation.

 

 

ADVANTAGE OF PBMCCDX AND PBMCPDX AT YICON

 

 

 

APPLICATION IN DRUG DEVELOPMENTS

 

1. Application of PBMCCDX and PBMCPDX in preclinical of I-O therapeutics development

 

a. CD3 modulators (eg. anti-CD3-based bispecific antibody and BiTE)

 

 

Fig.1 In vivo efficacy of anti-CD3-based bispecific antibody in PBMC humanized Herceptin resistant BT474 xenograft model

Left. Tumor growth curve of PBMC humanized Herceptin resistant BT474 xenografts treated with vehicle, anti-CD3 bispecific antibody and Herceptin, respectively. (data representsmean tumor volume ± SEM.) Middle. Percentage of human CD45+ leukocytes in peripheral blood of humanized mice. Right. HER2 expression in PBMC humanized Herceptin resistant xenografts by IHC.

 

 

 

Fig.2 In vivo anti-tumor activity of CD3/CD19 targeted BiTEs in PBMC humanized systemic leukemia NALM-6 in vivo imaging tumor model

a. Luciferase transfected NALM-6 leukemia cells were iv inoculated into NSG mice, and tumor growth was monitored weekly for 3 weeks by in vivo imaging. b. Kaplan-Meier survival curves of three treatment groups.

 

 

b. Test of other I-O agents

 

 

Fig.3 In vivo efficacy of both anti-PD-1 and anti-PD-L1 in PBMC humanized xenograft tumor models (A375, HUH-7 and MDA-MB-231)

 

 

2. Application of PBMCCDX and PBMCPDX in clinical evaluation of I-O therapeutic regimens   

 

 

Fig.4 Anti-tumor activity of Keytruda treatment alone and combined with palbociclib in advanced melanoma 

a. Tumor growth curves of PBMC humanized melanoma patient-derived xenograft (PDX) MELA005 mice treated with vehicle, palbociclib, Keytruda alone and Keytruda combined with palbociclib, respectively. (data represents mean tumor volume ± SEM.) b. The data published in clinical cancer research.

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