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Anti-CD171 CAR-T preclinical in vivo Assay

Target Background

CD171, also known as L1-CAM,is an axonal glycoprotein that belongs to the immunoglobulin superfamily proteins. It contains several immunoglobulin-like domains and fibronectin-like repeats (type III). CD171 plays an important role in nervous system development such as neuronal migration and differentiation, which are involved in axon guidance and cell migration with a strong implication in treatment-resistant cancers.

Anti-CD171 CAR-T preclinical in vivo Assay

Anti-CD171 CAR-T Cell Therapy

Originally reported to be enriched in neuroblastoma, CD171 is also highly expressed on many other solid tumors including melanoma and carcinomas of the cervix, ovary and bladder, which makes it an attractive target for the cellular-based therapy recently. CAR-redirected cytolytic T cells that specifically targeting the CE7 epitope of CD171 have been adopted in numerous studies including a Phase I clinical trial (NCT02311621) that is currently recruiting participants with primary recurrent/refractory neuroblastoma for the determination of the MTD of anti-CE7R CAR-T cells expressing EGFRt. In addition, evidence show that a diverse array of human tumor cell lines and primary solid tumors (ovarian, lung, and renal carcinoma, and glioblastoma) do express the CE7 epitope and can efficiently stimulate anti-CE7R T-cell lytic activity and secretion of pro-inflamatory cytokines. On the contrary, limited number of normal tissues (such as human monocytes) express CD171 antigen, which makes them unable to be recognized by the CE7 mAb or be targeted by anti-CE7R CAR-T cells, suggesting the tumor restriction of CE7 epitope as well as its potential for adoptive immunotherapy.

Animal Models for in vivo Study of anti-CD171 CAR-T Cell Therapy

Intracranial neuroblastoma model can be generated by intracranially injecting (2mm lateral, 0.5mm anterior to the bregma and 2.5mm deep to the dura) with firefly luciferase-expressing SK-N-DZ cells into the immune deficient NSG mice. Intervention starts after tumor formation via intra-tumoral injection of mock transduced or anti-CD171 CAR-T cells. Bioluminescent imaging and clinical observation will proceed regularly. Mice will be subjected to euthanasia when moribund appears.
Intraperitoneal ovarian cancer model can be established by inoculating luciferase - tagged human SKOV3 cells into the peritoneal cavity of CD1 nu/nu mice or BALB/c nu/nu mice. Anti-CD171 CAR-T cell intervention initiates when BLI signals reach between 10^7 to 10^8 photons/s. Professional disease monitoring will be proceed regularly and euthanasia will be executed when ascites or moribund (weight loss of >15% combined with behavioral signs of distress) appears.
Xenograft models for other solid tumors such as lung cancer, renal carcinoma, and glioblastoma are also available at Creative Biolabs. Tremendous storage of both cancer cell lines and patient primary samples will give you access to the selection of anti-CD171 CAR-T intervention responsive tumor cells and ensure your success of modeling as well.

In Vivo Assays Parameters and Techniques

At Creative Biolabs, we offer the most exquisite and comprehensive service platform for preclinical anti-CD171 CAR-T cell therapy research.
Efficacy Test
Tumor remission monitored by bioluminescence imaging (BLI)
FACS analysis
Survival curve tracking
Immuofluorescent microscopy
Immunohistochemistry
Viability and Bio-distribution Studies
Tumor infiltration, CAR-T cell durability, GLP-compliant bio-distribution studies
Cytokine release analysis (analysis of the pre- and post-infusion plasma samples)
Toxicity Evaluation
Pilot tolerability (MTD, the route of administration, dose regimen / response / onset)
Clinical observation (body weight, behavior, feed consumption)
Complete blood counts (CBC) and serum chemistry
Complete necropsy/organ weight
Histopathological 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 is professional in the R&D for CAR-T therapy. We cover both CAR-T development and preclinical in vivo studies including premier efficacy test on mice and further safety evaluation on NHP models. Our all-around service will render you priority of access to the clinical trials.

References

  1. Künkele, et al. "Preclinical Assessment of CD171-Directed CAR-T Cell Adoptive Therapy For Childhood Neuroblastoma: CE7 Epitope Target Safety and Product Manufacturing Feasibility." American Association for Cancer Research (2016): clincanres-0354.
  2. Wolterink, et al. "Therapeutic antibodies to human L1CAM: functional characterization and application in a mouse model for ovarian carcinoma."Cancer research 70.6 (2010): 2504-2515.

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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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