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Anti-Thyroglobulin (Tg) CAR-T Preclinical in vivo Assay

Target Background

Thyroglobulin (Tg) is a 660 kDa glycoprotein homodimer, which is produced predominantly by the follicular cells (thyrocytes) of the thyroid gland and ultimately metabolized within the liver. Physiologically, Tg acts as a substrate for the synthesis of thyroid hormones like thyroxine (T4) and triiodothyronine (T3). Meanwhile, Tg accounts for approximately half of the protein content of the thyroid gland and the breakdown of Tg releases iodine, so it also functions as storage of the inactive form of iodine for breast, stomach, salivary glands, thymus, choroid plexus and cerebrospinal fluid, etc. Normally, Tg is mainly located in the thyroid gland and circulating between the thyroid gland and the liver via blood. Previous studies proved that the elevation of the Tg level in the blood is an indication of thyroid cancer, primarily papillary or follicular thyroid carcinoma, which makes it a specific marker for the most common endocrine tumor with increasing incidence. Furthermore, the restrict expression of Tg in follicular cells makes it an unparalleled target for CAR-T therapy against papillary and follicular thyroid carcinoma while excludes medullary or anaplastic thyroid carcinoma.

Biosynthesis of thyroid hormones from thyroglobulin by thyroid peroxidase and regioselective deiodination of thyroxine

Biosynthesis of thyroid hormones from thyroglobulin by thyroid peroxidase and regioselective deiodination of thyroxine
Accounts of chemical research 46.11 (2013): 2706-2715

Anti-Thyroglobulin (Tg) CAR-T Cell Therapy

Recently, a pilot clinical study of adoptive cell transfer for the treatment of metastatic cancer has been designed to determine the safety and tolerability of the administration of anti-thyroglobulin mTCR-transduced autologous peripheral blood lymphocytes in human leukocyte antigen HLA-A2 positive patients with metastatic cancer (NCT02774291). The virgin land of anti-Tg CAR-T cell therapy will attract intensive research interest to initiate the very first pre-clinical and clinical studies. Creative Biolabs will help you set off the voyage to create the first anti-CD38 CAR-T cell therapy in the world.

Animal Models for in vivo Study of anti-Thyroglobulin (Tg) CAR-T Cell Therapy

Since the mouse strain B6C3F1 has a very low incidence of spontaneous thyroid cancer development, Creative Biolabs makes versatile animal models for thyroid cancer with the three strategies:

  1. Carcinogenic compounds: goitrogens are generally applied for inducing follicular neoplasm by decreasing thyroid hormone levels, elevating TSH and causing goiter development;
  2. Implantation of tumor cells: implant cultured human cell lines via a subcutaneous or orthotopic route in immunodeficient (SCID) and athymic (nude) mouse strains;
  3. Genetically engineered models: transgenic mice develop thyroid cancer via mutations or knock-in within TSH receptor (TSHR)-mediated signaling and mitogen-activated protein kinase (MAPK) pathways:
    1. Mouse models of papillary thyroid cancer: RET/PTC1, BRAFV600E, TRK-T1, H-RasG12V, Prkar1adelta2/+;
    2. Mouse models of follicular thyroid cancer: K-RasG12V, N-RasGln61Lys, K-RasG12DPten-/-, TRβPV/PV, α1b-adrenergic receptor, Rap1bG12V.

In addition, Creative Biolabs also assists customers in creating clinically relevant orthotopic mouse models including but not limited to the above categories.

In vivo Assay Parameters and Techniques

At Creative Biolabs, we offer the most exquisite and comprehensive service platform for preclinical Thyroglobulin (Tg) CAT-T cell therapy research.
Efficacy Test
Tumor remission monitored by tumor volume recording or bioluminescence imaging and survival curve tracking
Viability and Bio-distribution Studies
Durability, GLP-compliant bio-distribution studies
Toxicity Evaluation
Pilot tolerability (MTD, The route of administration, Dose regimen/response/onset)
Clinical observation (body weight, feed consumption, ophthalmologic and clinical pathology)
Cytokine storm surveillance (fever, hypertension, prolonged cytopenia)
Complete necropsy, organ weight
Histopathology
Tumorigenicity study

Creative Biolabs accurately senses and predicts the micro-area of research treasure, and intends to establish more reliable and subtle animal models in advance to help customer fulfill the rigorous requirements of preclinical studies masterly. Creative Biolabs assists researchers in making the scientific history.

References

  1. Kashat, Lawrence, et al. "Serial post-surgical stimulated and unstimulated highly sensitive thyroglobulin measurements in low- and intermediate-risk papillary thyroid carcinoma patients not receiving radioactive iodine."Endocrine (2016): 1-7.
  2. Manna, Debasish, Gouriprasanna Roy, and Govindasamy Mugesh. "Antithyroid drugs and their analogues: synthesis, structure, and mechanism of action." Accounts of chemical research 46.11 (2013): 2706-2715.

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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
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Tel: 44-207-097-1828

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