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Anti-PSMA CAR-T Preclinical in vivo Assay

Target Background

PSMA (prostate-specific membrane antigen), well known as FOLH1 (folate hydrolase 1) or GCP II (glutamate carboxypeptidase II), encodes a type II transmembrane glycoprotein belonging to the M28 peptidase family. As a zinc metalloenzyme, PSMA residing in membrane catalyzes the hydrolysis of N-acetylaspartylglutamate (NAAG) to glutamate and N-acetylaspartate (NAA), also other alternative substrates like nutrient folate. Normally, PSMA is mainly expressed in the prostate epithelium (roughly a hundred times greater than in most other tissues), the proximal tubules of the kidney, the je jubal brush border of the small intestine and ganglia of the nervous system. As for human malignancies, PSMA is elevated in prostate cancer with an 8- to 12-fold increase over noncancerous prostate cells, which accounts for almost a thousand times increase over most other normal tissues. Meanwhile, high level of PSMA correlates with the aggressiveness of human malignancies. In addition, PSMA is also highly expressed in tumor neovasculature excluding corresponding normal vasculature of all types of solid tumors such as kidney, breast, colon, etc. Therefore, PSMA manifests as a wonderful target with the most minimal tissue penetration, and is suitable for the development of anti-PSMA CAR-T cell therapy.

Structure of inactive PSMA mutant in complex with β-citryl glutamate

Structure of inactive PSMA mutant in complex with β-citryl glutamate
Diagram created by Creative Biolabs based on data from The FEBS journal 283(2016): 2528-2545

Anti-PSMA CAR-T Cell Therapy

Despite the multiple PET/CT trials targeting on PSMA, the two phase 1 clinical trials (NCT01414283, NCT01414296) are conducted for PSMA antibody-drug conjugate 1301 in subjects with progressive, castration-resistant, metastatic prostate cancer. Furthermore, several phase 1/2 pilot studies (NCT01929239, NCT01140373 and NCT00664196) are aiming at the adoptive transfer of autologous anti-PSMA designer T cells for the treatment of prostate cancers. Creative Biolabs helps researchers surpass the entire existing achievements of anti-PSMA CAR-T cell therapy to a whole new level.

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

Creative Biolabs offers researchers almost all the animal models generated from the major techniques including the conventional carcinogen-induced models, the mosaic transposon- or virus-induced models, the transgenic models and the subcutaneous or patient-derived xenograft models for a variety of human malignancies. Below is the 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)

In addition, Creative Biolabs also assists customers in creating clinically relevant animal models including but not limited to the above categories. You request, Creative Biolabs offers the best.

In vivo Assay Parameters and Techniques

At Creative Biolabs, we offer the most exquisite and comprehensive service platform for preclinical PSMA 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. Lütje, Susanne, et al. "Targeting human prostate cancer with 111In‐labeled D2B IgG, F (ab′) 2 and Fab fragments in nude mice with PSMA‐expressing xenografts." Contrast media & molecular imaging 10.1 (2015): 28-36.
  2. Crowley, Michael JP, et al. "Prostate-specific membrane antigen is a potential antiangiogenic target in adrenocortical carcinoma." The Journal of Clinical Endocrinology & Metabolism 101.3 (2016): 981-987.
  3. Navrátil, Michal, et al. "Comparison of human glutamate carboxypeptidases II and III reveals their divergent substrate specificities." The FEBS journal 283(2016): 2528-2545.
  4. Valkenburg, Kenneth C., and Bart O. Williams. "Mouse models of prostate cancer." Prostate cancer 2011 (2011).

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CONTACT US

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45-1 Ramsey Road, Shirley, NY 11967, USA
Tel: 1-631-871-5806
Fax: 1-631-207-8356
Email:

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Tel: 44-207-048-3343

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