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Anti-IL13Rα2 CAR-T Preclinical in vivo Assay

Target Background

Interleukin-13 receptor α2 (IL13Rα2) is a cell surface receptor mostly found on glioma but limited on normal cells.  In oncology, expression of IL13Rα2 indicates poor survival of patients with glioblastoma. IL13 normally binds to IL13Rα1 and forms IL13Rα1-IL13 complex that attaches to IL4Rα. This complex has been shown to be able to promote cell apoptosis mechanism by activating STAT6. However, tumor cell can escape from this cell death mechanism via expression of IL13Rα2, which has stronger binding affinity to IL13 compared to IL13Rα1. Therefore, selectively expressed IL13Rα2 has been considered as one of the potential immunotherapeutic targets for cancer treatment, especially glioblastoma.

Anti-IL13Rα2 CAR-T Preclinical in vivo Assay

Significance of interleukin-13 receptor alpha 2–targeted glioblastoma therapy.
Neuro-Oncology,2014. 16(10), 1304-1312.

Anti-IL13Rα2 CAR-T Cell Therapy

After clinical trials of first generation anti-IL13Rα2 CAR-T cells, second generation CARs are developed to improve antitumor potency and persistence of T cells. These CAR-T cells belong to central memory T cell population and contain CD137 costimulatory signaling domain (IL13BBζ). Results from preclinical experiments indicate that intracranial-administrated anti-IL13BBζ CAR-T cells efficiently inhibit brain tumor growth at primary carcinoma site and track tumor cells to contralateral hemisphere. Moreover, this delivery method seems to be more potent than intravenous injection of anti-IL13Rα2 CAR-T cells. Currently, another Phase I clinical trial of anti-IL13Rα2 CAR-T cells for patients with glioblastoma are being conducted (NCT02208362). Early data from this trial shows local delivery of anti-IL13Rα2 CAR-T cells are safe and antitumor activity in patients is observed.

Animal Models for in vivo Study of anti-IL13Rα2 CAR-T Cell Therapy

Creative Biolabs provides well-established in vivo tumor models for evaluation of anti-IL13Rα2 CAR-T cells. All animals are maintained in a clean and feed enriched environment before experiments. Our experienced scientist group has extensive knowledge and expertise in animal experiments.
Xenograft model of glioblastoma
Immunodeficiency ICR-SCID mice are anesthetized throughout procedure and immobilized in stereotactic apparatus. IL13Rα2+ GMB cells are injected along small burr-hole, which is 1mm deep into skull and 2mm to right of bregma. Tumor bearing mice are treated with anti-IL13Rα2 CAR-T cells through same incision after 10 days of tumor growth. Animals are euthanized when tumor sizes reach certain criteria. Pain control is given to mice after model establishment (subcutaneous injection of buprenorphine) if necessary.

In vivo Assay Parameters and Techniques

Creative Biolabs offers comprehensive services to evaluate anti-IL13Rα2 CAR-T cell therapy. Our technical group is very experienced and efficient in data production. Experimental techniques can be customized at clients’ request or purpose-orientated.
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.

Scientists at Creative Biolabs are highly experienced and equipped with state-of-the-art facilities. We fully understand that researches of CAR-T therapy targeting IL13Rα2 is a time-consuming and costly process. We would like to provide a wide range of services to assist you and your team to accelerate this process.

References

  1. Brown, et al. "Adoptive transfer of IL13Rα2-specific T cells for the treatment of glioblastoma: building on clinical achievements with second-generation CARs." Journal for immunotherapy of cancer 1.1 (2013): 1.
  2. Thaci, et al. "Significance of interleukin-13 receptor alpha 2–targeted glioblastoma therapy." Neuro-oncology (2014): nou045.

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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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