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Anti-Igκ CAR-T Preclinical in vivo Assay

Target Background

Antibody or immunoglobulin (Ig) is typically composed of two light chains and two heave chains. In human and other mammals, there are two classes of light chains, namely kappa (κ) chain and lambda (λ) chain. Once set, each B lymphocyte can express only one type of light chains. Antibody is the secreted form of the B cell receptor. Thus, B cells, as well as B cell malignancies, express either κ chain or λ chain on cell surface. Taking advantage of this clonal restriction characteristic, scientists intend to target the κ chain positive lymphoma cells with the normal B cells that express the reciprocal λ chain not affected. The impairment to humoral immunity is therefore minimized. While targeting pan-B cell markers (such as anti-CD19 CAR-T therapy) usually causes depletion of normal B cells and results in severe hypogammaglobulinemia.

Anti-Igκ CAR-T Preclinical in vivo Assay

Anti-Igκ CAR-T Cell Therapy

It was reported that anti-Igκ CAR-T cells showed cytotoxic activity against Igκ positive tumor cell lines and primary low-grade lymphoma and chronic lymphocytic leukemia (B-CLL) cells both in vitro and in vivo. Patients with refractory or relapsed CLL and non-Hodgkin lymphoma (NHL) are treated with anti-Igκ CAR-T cells in a phase I trial. These CAR-T cells are well-tolerated without adverse effects. The molecular signals of CAR peak at about 1 to 2 weeks after infusion and remain detectable for at least 6 weeks and up to 9 months. Two of five patients with relapsed NHL entered complete remission and three of three patients with multiple myeloma had stable disease associated with reduction of paraprotein, while two of two patients with CLL both progressed. These data confirm the safety and efficacy of anti-Igκ CAR-T cells therapy.

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

We have established multiple animal models for the in vivo assay of anti-Igκ CAR-T cells. Different kinds of Igκ+ cells such as Daudi, JEKO-1, BJAB, CCL-120 cell lines, human primary CLL cells and some Igκ+ transfected cell lines are injected subcutaneously, intraperitoneally, or intravenously in SCID mice to induce a tumor in the mice. CAR-T treatment is applied when tumor progression reaches certain criteria. 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 for anti-Igκ 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.

As a frontier biotech service provider, Creative Biolabs has plenty of expertise and experience in the CAR-based therapy development. We now provide preclinical in vivo assay service to support your research on anti-Igκ CAR-T development. Our one-stop service package includes the development of animal models and the evaluation of efficacy, safety, viability and bio-distribution of anti-Igκ CAR-T cells.

References

  1. Savoldo, et al. "Clinical responses in patients infused with T lymphocytes redirected to target κ-light immunoglobulin chain." Blood 122.21 (2013): 506-506.
  2. Vera, et al. "T lymphocytes redirected against the κ light chain of human immunoglobulin efficiently kill mature B lymphocyte-derived malignant cells." Blood 108.12 (2006): 3890-3897.

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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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