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Anti-PSCA CAR-T Preclinical in vivo Assay

Target Background

PSCA (prostate stem cell antigen) or PSA (prostate-specific antigen), also known as gamma-seminoprotein or kallikrein-3 (KLK3), encodes a glycosylphosphatidylinositol-anchored cell membrane glycoprotein belonging to the kallikrein-related peptidase family, which is almost exclusively expressed and secreted by the epithelial cells in the prostate for its namesake, as well as in the bladder, placenta, colon, kidney and stomach. Physiologically, PSCA functions as a serine protease to liquefy semen in the seminal coagulum and dissolve cervical mucus to liberate sperm and allow entry into the uterus. Pathologically, PSCA is up-regulated in a large proportion of prostate, bladder and pancreas cancers, especially of primary and metastatic prostate cancers. In the United States, the U. S. Food and Drug Administration (FDA) has approved the PSCA test for annual screening of prostate cancer in men of age 50 and older. On account of the unparalleled role in promoting the growth and metastasis of prostate cancer, and the extremely restricted expression in the prostate, PSCA is manifested as an important diagnostic marker and a promising therapeutic target for a safer and more effective immunotherapy.

Structure of PSA complex with a substrat-acyl intermediate and an activating antibody

Structure of PSA complex with a substrat-acyl intermediate and an activating antibody
Diagram created by Creative Biolabs based on data from Journal of molecular biology 376.4 (2008): 1021-1033

Anti-PSCA CAR-T Cell Therapy

Since T cells genetically engineered with a chimeric antigen receptor (CAR) has been successfully applied on several human malignancies, two phase 1 clinical trials (NCT02744287 and NCT01140373) have been designed to test the feasibility and safety of anti-PSCA chimeric antigen receptor engineered T cells in subjects with non-resectable pancreatic cancer and castrate metastatic prostate cancer respectively. Creative Biolabs will help researchers create and perform the most cutting-edge anti-PSCA CAR-T cell therapy in the world.

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

Creative Biolabs endows researchers with versatile laboratory and clinical animal models of all human malignancies. Below is an example of transgenic mouse models of prostate cancer.

Transgenic mouse and organ models of prostate cancer

Transgenic mouse and organ models of prostate cancer
Prostate cancer 2011 (2011)

Creative Biolabs assists customers in creating clinically relevant animal 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 PSCA 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 outperforms the entire biotechnological community to back researchers with every resource for establishing the most reliable and subtle animal models in advance to help the customer achieve incredible disproportionate results and exponentially greater value. Creative Biolabs assists researchers in making the scientific history.

References

  1. Kim, Sung Han, et al. "Prostate stem cell antigen expression in radical prostatectomy specimens predicts early biochemical recurrence in patients with high-risk prostate cancer receiving neoadjuvant hormonal therapy." PloS one 11.3 (2016): e0151646.
  2. Ménez, Renée, et al. "Crystal structure of a ternary complex between human prostate-specific antigen, its substrate-acyl intermediate and an activating antibody." Journal of molecular biology 376.4 (2008): 1021-1033.
  3. Hillerdal, Victoria, et al. "Systemic treatment with CAR-engineered T cells against PSCA delays subcutaneous tumor growth and prolongs survival of mice." BMC cancer 14.1 (2014): 1.
  4. Valkenburg, Kenneth C., and Bart O. Williams. "Mouse models of prostate cancer." Prostate cancer 2011 (2011).

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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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Tel: 44-207-097-1828

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