Anti-Lewis^Y CAR-T Preclinical In Vivo Assay

All products and services are For Research Use Only and CANNOT be used in the treatment or diagnosis of disease.

Target Background

Lewis^Y 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 Lewis^Y is formed by addition of a α1, 3-linked fucose residue to the structure of blood group H antigen. The expression level of Lewis^Y 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 Lewis^Y antigen is also found in the sera of both normal donors and cancer patients. Several groups have tested therapeutic vaccines against the Lewis^Y epitope but only limited success has been achieved due to the weak immunogenicity of Lewis^Y. Monoclonal antibodies and antibody-drug candidates (ADCs) targeting Lewis^Y are also being intensively studied.

Anti-LewisY CAR-T Preclinical in vivo Assay

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

Anti-Lewis^Y CAR-T Cell Therapy

In a Phase I clinical trial of anti-Lewis^Y CAR-T cell therapy, five patients with relapsed AML were involved. After chemotherapy preconditioning, the patients were infused with anti-Lewis^Y 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 Lewis^Y 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-Lewis^Y 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-Lewis^Y CAR-T Cell Therapy

We have established multiple animal models for the in vivo assay of anti-Lewis^Y CAR-T cells. Different kinds of Lewis^Y 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-Lewis^Y 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-Lewis^Y CAR-T cells.

References

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.
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.
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.
Brenner, et al. "CAR T cells for acute myeloid leukemia: the LeY of the land." Molecular Therapy 21.11 (2013): 1983.
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.

Anti-LewisY CAR-T Preclinical In Vivo Assay

Anti-Lewis^Y CAR-T Preclinical In Vivo Assay