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Anti-CD133 CAR-T Preclinical in vivo Assay

Target Background

CD133 (prominin-1) is a transmembrane glycoprotein specifically encoded by the PROM1 gene. It is expressed on many types of cells in human including many tumor entities such as brain tumors and melanomas. A CD133+ cell population is also considered as a cancer stem cell (CSC) population that possesses the capacity for self-renewal and differentiation. In addition, CD133+ melanoma cells are immunogenic and can be used as an anti-melanoma vaccination, which has been proven to induce strong anti-tumor activity. Studies have shown that AC133, an N-glycosylation-dependent epitope of CD133, is almost exclusively stem cell specific and has been described as a CSC marker for a large variety of brain and extracranial tumors, despite the fact that CD133 is per se not stem cell specific. For this reason, AC133 is now considered to be a potential immunotherapeutic target against CD133+ tumors, such as prototypic glioblastoma multiforme.

Anti-CD133 CAR-T Preclinical in vivo Assay

Anti-CD133 CAR-T Cell Therapy

Clinical trials pointing to anti-CD133 CAR-T therapy have started enrolling recently for the treatment of relapsed and/or chemotherapy refractory advanced malignancies including liver cancer, pancreatic cancer, brain tumor, breast cancer, ovarian tumor, colorectal cancer, acute myeloid and lymphoid leukemia (NCT02541370). In addition, CAR-T design based on AC133 epitope of CD133 also shows anti-tumor effects on glioblastoma. At the same time, research emphasis on how to extend CAR-T cell persistence that was relatively short in previous studies to achieve complete disease recovery. Creative Biolabs possesses the most exquisite techniques on CAR-T development and animal in vivo studies, which will facilitate our customers’ requirement on the construction and remodeling of anti-CD133 CAR-T cells as well as related preclinical tests.

Animal Models for in vivo Study of anti-CD133 CAR-T Cell Therapy

Orthotopic xenograft models for glioblastoma are established via intracranial implantation of luciferase-expressing NCH421K human glioblastoma cells. The BLI signals from tumors are measured regularly, usually every other day. Anti-CD133 CAR-T cells or non-transfected T cells will be injected via the original injection hole when BLI signals reaches between 107 to 108 photons/s. Animals are regularly checked for health conditions and euthanized when emaciation or neurological deficits appear.
Xenograft models for relapsed and/or chemotherapy refractory advanced malignancies including brain cancer, melanoma, glioblastoma, liver cancer, pancreatic cancer, breast cancer, ovarian cancer, colorectal cancer, acute myeloid and lymphoid leukemia are developed by our experienced team during the in vivo study. Both disseminated and orthotopic animal models are available in Creative Biolabs, and our full-fledged service platforms will meet customers’ requirement in the anti-CD133 CAR-T investigation.

In vivo Assay Parameters and Techniques
At Creative Biolabs, we offer the most exquisite and comprehensive service platform for anti-CD133 CAR-T cell therapy research.
Efficacy Test
Combinatorial or trans-signaling CAR strategies
Tumor remission monitored by bioluminescence imaging (BLI)
FACS analysis
Survival curve tracking
Immuofluorescent microscopy
Viability and Bio-distribution Studies
Tumor infiltration, durability, GLP-compliant bio-distribution studies
Toxicity Evaluation
Pilot tolerability (MTD, the route of administration, dose regimen / response / onset)
Clinical observation (body weight, behavior, feed consumption)
Complete necropsy/organ weight
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.

At Creative Biolabs, we aim at establishing the most reliable tumor models and the most accurate research procedures by keeping up with technology pace along CAR-T in vivo study. In addition, we insist on continuously expanding our service platforms, aiming to bridge the gap between the early development and the clinical application of CAR-T cell therapy.

References

  1. Zhu, et al. "Patient-derived glioblastoma stem cells are killed by CD133-specific CAR-T cells but induce the T cell aging marker CD57."Oncotarget 6.1 (2015): 171-184.

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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:

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

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