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Anti-NY-ESO-1 CAR-T Preclinical in vivo Assay

Target Background

NY-ESO-1 is known as a cancer/testis antigen and widely expressed in 10% to 50% of various tumors of different origins including prostate, breast, lung, melanoma, thyroid, squamous head and neck, as well as 70% to 80% of synovial cell sarcomas. Moreover, NY-ESO-1 expression is only restricted in adult testis and absent in normal somatic cells. Recent studies demonstrate that highly expressed NY-ESO-1 is mostly found in patients with relapsing multiple myeloma (MM) or cytogenetic abnormality. Spontaneous NY-ESO-1 antibodies and specific T cells are detected in NY-ESO-1 positive patients, which indicate NY-ESO-1 as a potent target for anti-MM immunotherapies.

Anti-NY-ESO-1 CAR-T Cell Therapy

A number of pilot clinical trials have been initiated for evaluation NY-ESO-1 specific CAR-T therapies in patients with different carcinomas. A phase I/II clinical trial reports that NY-ESO-1 targeted T cells showed encouraging responses to multiple myeloma patients receiving autologous stem cell transplant. These results suggest that the engineered T cells are safe and have extended persistence correlated with clinical activity.

Anti-NY-ESO-1 CAR-T Preclinical in vivo Assay

Mechanisms of action of therapeutic antibodies for cancer.
Molecular Immunology,2015. 67(2), 28-45.

Animal Models for in vivo Study of anti-NY-ESO-1 CAR-T Cell Therapy

Our technical team has extensive knowledge and experience for in vivo model development. All animal experiments are monitored under an approved Institutional Animal Care and Use Committee (IACUC) protocol. Creative Biolabs provides various xenograft models of human carcinoma.  
Human colon carcinoma model
Colon carcinoma cells CT26 are transfected to stably express NY-ESO-1 and subcutaneously injected into immunocompromised mice in right or left flank, followed by CAR-T cells treatment when tumor sizes meet certain criteria.
Xenograft model of human myeloma
NOD/SCID mice receive MM cell U266 or U266/Luc expressing cells via tail vein injection (or subcutaneous injection) and engineered T cells in same administration route. Tumor growth is monitored by intraperitoneally injection of D-luciferin and read in image xenograft imaging system.

In vivo Assay Parameters and Techniques

Creative Biolabs offers comprehensive services to test NY-ESO-1 targeted CAR-T therapy in preclinical tests. All tests are conducted by well-trained technicians and strike to milestone of timeline.
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.

Creative Biolabs fully understands researches of adoptive T cell therapy targeting NY-ESO-1 are time-consuming and costly. With our highly experienced technical groups and state-of-the-art facilities, we can accelerate these studies by providing our top-quality in vivo tumor models and efficient analyzing services.

References

  1. Schuberth, et al. "Effector memory and central memory NY-ESO-1-specific re-directed T cells for treatment of multiple myeloma." Gene therapy20.4 (2013): 386-395.
  2. Scanlan, et al. "Cancer/testis antigens: an expanding family of targets for cancer immunotherapy." Immunological reviews 188 (2002): 22-32.

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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: 44-207-048-3343

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