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Anti-CD19 CAR-T Preclinical in vivo Assay

Target Background

CD19 is a B cell surface protein expressed throughout B cell development. It is expressed on nearly all B cell malignancies including acute lymphoblastic leukemia (ALL), chronic lymphocytic leukemia (CLL), and many non-Hodgkin lymphoma (NHL), while not expressed in hematopoietic stem cells. This specificity and universal expression for a single cell lineage make CD19 a very attractive target for CAR-T based cell therapy. Immunologic targeting of CD19 carries a minimal risk of bone marrow (BM) toxicity or autoimmunity other than the potential induction of B-cell aplasias.

Anti-CD19 CAR-T Cell Therapy

Currently, anti-CD19 CAR-T cell therapies for B-cell malignancies are the most advanced engineered T cell therapies being tested. Clinical trials in ALL and CLL have exhibited robust and striking clinical efficacy. And, in several reports, anti-CD19 CAR-T cell therapies induced remissions in some patients with considered incurable relapsed, highly refractory ALL, refractory, bulky CLL and NHL. Despite these positive results, Anti-CD19 CAR-T therapy still has some risks in clinical applications, such as high level of inflammatory cytokines and B-cell aplasia.

Animal Models for in vivo Study of anti-CD19 CAR-T Cell Therapy

We have successfully established multiple animal models for the in vivo assay of anti-CD19 CAR-T cells. Various kinds of CD19+ cells, such as human ALL or CLL cells, NALM-6 pre-B cell ALL cell line, Raji Burkitt lymphoma cell line, Daudi Burkitt lymphoma cell line, and some CD19 transfected cell lines are used depending on different requirements of customers. Tumor cells are injected subcutaneously, intraperitoneally, or intravenously to set up different tumor models in animals. In our past investments, NOD/SCID/γc-/- mice, NOD/SCID/β2-/- mice, and SCID-Beige mice (Fox Chase C.B-17) were all involved. Rats and non-human primates (NHPs) are also available.

In vivo Assay Parameters and Techniques

At Creative Biolabs, we offer the most exquisite and comprehensive service platform for anti-CD19 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.

Preclinical assessments of CAR-T safety are necessary for its risk managements. Besides, the efficacy and pharmacokinetic characteristics of CAR-T cells should be tested in animal models for CAR optimization and dosage determination. As a frontier biotech service provider, Creative Biolabs is pleased to share its extensive experience acquired during the development of CAR-T technology.

Anti-CD19 CAR-T Preclinical in vivo Assay

References

  1. Brentjens, et al. "Safety and persistence of adoptively transferred autologous CD19-targeted T cells in patients with relapsed or chemotherapy refractory B-cell leukemias." Blood 118.18 (2011): 4817-4828.
  2. Brentjens, et al. "Genetically targeted T cells eradicate systemic acute lymphoblastic leukemia xenografts." Clinical cancer research 13.18 (2007): 5426-5435.
  3. Kochenderfer, et al. "Construction and Pre-Clinical Evaluation of An Anti-CD19 Chimeric Antigen Receptor." Blood 112.11 (2008): 4623-4623.
  4. Kochenderfer, et al. "Treating B-cell cancer with T cells expressing anti-CD19 chimeric antigen receptors." Nature reviews Clinical oncology 10.5 (2013): 267-276.
  5. Maude, et al. "CD19-targeted chimeric antigen receptor T-cell therapy for acute lymphoblastic leukemia." Blood 125.26 (2015): 4017-4023.
  6. Milone, et al. "Chimeric receptors containing CD137 signal transduction domains mediate enhanced survival of T cells and increased antileukemic efficacy in vivo." Molecular Therapy 17.8 (2009): 1453-1464.
  7. Xu, et al. "Closely related T-memory stem cells correlate with in vivo expansion of CAR. CD19-T cells and are preserved by IL-7 and IL-15." Blood123.24 (2014): 3750-3759.

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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: 44-207-097-1828

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