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Anti-FAP CAR-T Preclinical in vivo Assay

Target Background

Fibroblast activation protein α (FAP) is a 170kDa transmembrane type 2 dipeptidyl peptidase that cleaves substrate at a post-proline bond. FAP was firstly identified in cancer-associated fibroblast, and following researches indicate that expression of FAP is observed in most epithelial cancers such as colon, breast, pancreatic, skin and lung cancer, as well as in embryo, healing wound, and chronic inflammatory and fibrotic tissues. However, expression level of FAP is very low or undetectable in other fibroblast of adults, which makes FAP a potential target for CAR-T based cell therapy. Previous studies indicate that FAP-targeted vaccines and immunoconjugate therapies are able to inhibit tumor growth and have no obvious toxicity in wound healing.

Anti-FAP CAR-T Cell Therapy

Results of various preclinical studies has been published to support clinial trials of FAP re-directed CAR-T therapy for patient of malignant pleural mesothelioma. FAP-targeted T cells showed promising inhibition for FAP positive mesothelioma cells in peritoneal cavity and increased lifespan of tumor-bearing mice. A phase I clinical trial that evaluates anti-FAP CAR-T cells in patients with pleural mesothelioma has been initiated (NCT01722149).  Patients are treated with re-directed FAP-specific CAR-T cells in the pleural effusion. Safety monitoring will last for 35 days for each patients.

Anti-FAP CAR-T Preclinical in vivo Assay

Animal Models for in vivo Study of anti-FAP CAR-T Cell Therapy

Following in vitro studies of FAP-specific CAR-T cells, Creative Biolabs provides various human FAP-expressing cell lines for in vivo tumor model development and anti-FAP CAR-T cell efficacy evaluation. Cell lines that are being used include lung fibroblast cell (Hs894), prostate cancer-associated fibroblast cell (HPS-19I), jmelenoma (SENMA), nasopharyngeal carcinoma (C666.1), glioblastoma (U87) and pancreatice ductal carnimoma (PL45). We offer the most exquisite animal models with prominent expression of FAP including but not limited to the following categories.
Xenograft model of human squamous cell carcinoma
Athymic NMRI nude mice in age of 6 to 8 weeks are subcutaneously injected with human squamous cell line HTB-43 in the right or left flank. Tumor size is measured 3 times per week by direct measurement. Physiological signs, body weight, temperature and food consumption are recorded after infusion of FAP-targeted CAR-T cells.
Xenograft model of human pancreatic cancer
Rag1-deficient mice are given subcutaneous injections of human pancreatic adenocarcinoma cells and receive CAR-T cells via tail vein injection after 21 days.
Xenograft model of non-small cell lung cancer
Creative Biolabs provides SCID Beige mice as tumor bearing animals of non-small cell lung cancer. Cell line A549 is injected intravenously into mice and followed by intravenous injection of FAP-targeted CAR-T cells and intraperitoneal injection of human recombinant IL-2.

In vivo Assay Parameters and Techniques

Creative Biolabs offers comprehensive services to evaluate anti-FAP CAR-T efficacy. Our technical group is very experienced and strive to finish each milestone within proposed timeline.
Efficacy Tests
Tumor remission monitored by tumor volume recording or bioluminescence imaging and survival curve tracking.
Viability and Bio-distribution Studies
Durability and bio-distribution are evaluated by bioluminescence imaging, immunochemistry staining and real-time PCR
Toxicity Evaluation
Pilot tolerated evaluation: route of administration, dosage, MTD
Clinical observation: body weight, food consumption, behavior and pathological signs
Cytokine storm surveillance (fever, hypertension, prolonged cytopenia)
Postmortem analysis
Tumorigenicity study
GLP-Compliant Preclinical Test
All our experiments are performed by well-trained and experienced technicians in a GLP-compliant and IACUC-regulated facility.

Creative Biolabs fully understands that researches of adoptive T cell therapy targeting FAP are time-consuming and costly. With our highly experienced technical groups and state-of-art facilities, we are able to provide well-proved in vivo tumor models to accelerate research process of our clients.

References

  1. Wang, et al. "Targeting fibroblast activation protein in tumor stroma with chimeric antigen receptor T cells can inhibit tumor growth and augment host immunity without severe toxicity." Cancer immunology research 2.2 (2014): 154-166.
  2. Kakarla, et al. "Antitumor effects of chimeric receptor engineered human T cells directed to tumor stroma." Molecular Therapy 21.8 (2013): 1611-1620.

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CONTACT US

USA
45-1 Ramsey Road, Shirley, NY 11967, USA
Tel: 1-631-871-5806
Fax: 1-631-207-8356
Email:

Europe
Ringstrasse 4, 64401 Gross-Bieberau, Germany
Tel: 44-207-097-1828

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