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Anti-LewisY CAR-T Preclinical in vivo Assay

Target Background

LewisY antigen (CD174) is one type of tumor associated carbohydrate antigens (TACAs) from the so-called blood group antigen family found on human blood cells. The structure of LewisY is formed by addition of a α1, 3-linked fucose residue to the structure of blood group H antigen. The expression level of LewisY is very low in normal tissues, but it is highly expressed on about half of acute myeloid leukemia (AML) and multiple myeloma (MM) tumors; and on a subset of lung, ovarian, breast, prostate, colorectal, and gastric cancers. A soluble form of LewisY antigen is also found in the sera of both normal donors and cancer patients. Several groups have tested therapeutic vaccines against the LewisY epitope but only limited success has been achieved due to the weak immunogenicity of LewisY. Monoclonal antibodies and antibody-drug candidates (ADCs) targeting LewisY are also being intensively studied.

Anti-LewisY CAR-T Preclinical in vivo Assay

Cancer Vaccines and Carbohydrate Epitopes
Vaccine 29(48):8802-8826.

Anti-LewisY CAR-T Cell Therapy

In a Phase I clinical trial of anti-LewisY CAR-T cell therapy, five patients with relapsed AML were involved. After chemotherapy preconditioning, the patients were infused with anti-LewisY CAR-T cells. No major toxicity was observed in these patients. Three of the four patients who were evaluable achieved a reduction in their residual disease. However, ultimately all have relapsed. The AML blasts present at relapse kept to express LewisY antigen at a level comparable to the samples before treatment, suggesting that the progression does not result from antigenic shift. The trial also showed that the anti-LewisY CAR-T cells are able to home to the bone marrow and infiltrate into sites of disease. Although the results of this clinical trial are limited, the data proved that targeting non-protein TACAs in hematological malignancy and in solid tumors is feasible.

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

We have established multiple animal models for the in vivo assay of anti-LewisY CAR-T cells. Different kinds of LewisY positive cells such as MCF-7 (breast), PANC-89 (pancreas), OVCA R-3 (ovarian), HT29 (colorectal), MDA-MB-231 (breast), T47D (breast), A431 (epider moid), Hey (ovarian) cell lines and human primary AML cells are used to develop xenograft cancer models with NOD-SCID mice. We are also able to provide rats and non-human primates (NHPs) models to meet your special requirement.

In vivo Assay Parameters and Techniques

At Creative Biolabs, we offer the most exquisite and comprehensive service platform foranti-LewisY CAR-T cell therapy research.
Efficacy Test
Tumor remission monitored by tumor cell analysis 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
GLP-Compliant Preclinical Test
All our experiments are performed by well-trained and experienced technicians in a GLP-compliant and IACUC-regulated facility.

Developing CAR-based therapy requires high level of specialized support and expertise. Scientists from Creative Biolabs can help customers by providing CAR-T preclinical in vivo assay services that yield reliable results for CAR-based research. Our one-stop service package includes the development of animal models and the evaluation of efficacy, safety, viability and bio-distribution of anti-LewisY CAR-T cells.

References

  1. Westwood, et al. "Adoptive transfer of T cells modified with a humanized chimeric receptor gene inhibits growth of Lewis-Y-expressing tumors in mice." Proceedings of the National Academy of Sciences of the United States of America 102.52 (2005): 19051-19056.
  2. Neeson, P., et al. "Ex vivo culture of chimeric antigen receptor T cells generates functional CD8+ T cells with effector and central memory-like phenotype." Gene therapy 17.9 (2010): 1105-1116.
  3. Peinert, S., et al. "Gene-modified T cells as immunotherapy for multiple myeloma and acute myeloid leukemia expressing the Lewis Y antigen."Gene therapy 17.5 (2010): 678-686.
  4. Brenner, et al. "CAR T cells for acute myeloid leukemia: the LeY of the land." Molecular Therapy 21.11 (2013): 1983.
  5. Ritchie, et al. "Persistence and efficacy of second generation CAR-T cell against the LeY antigen in acute myeloid leukemia." Molecular Therapy 21.11 (2013): 2122-2129.

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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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