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Anti-CD22 CAR-T Preclinical in vivo Assay

Target Background

CD22 is a transmembrane phosphoglycoprotein that belongs to the Siglec family of lectins and specifically binds sialic acid with its N-terminus seven extracellular immunoglobulin domains. It mainly acts as an inhibitory receptor for B cell activation and signaling and regulates the interaction of B cells with T cells and antigen presenting cells (APCs). It is also involved in the B lymphocyte homing in mice. Similar to CD19, CD22 is a B cell lineage-restricted marker, expressed explicitly by B lymphoid cells from the pre-B to mature B cell stage. However, it is lost during differentiation to plasma cells. CD22 is universally expressed in most B cell malignancies, including acute lymphoblastic leukemia (ALL), chronic lymphocytic leukemia (CLL), and various subtypes of non-Hodgkin lymphoma (NHL) such as diffuse large B cell lymphoma. Therefore, CD22 is an attractive therapeutic target for B cell malignancies, which has been confirmed by the positive results in clinical trials of anti-CD22 monoclonal antibodies (epratuzumab) and immunotoxins (BL22, HA22). Anti-CD22 CAR-T cell therapies have also obtained robust and striking clinical efficacy. Notably, CD22 has been shown to be expressed on ALL cells that lost CD19 expression after treatment with anti-CD19 CAR-T cells, making anti-CD22 CAR-T cells a potential combination or follow-on therapy of anti-CD19 CAR-T cells.

Anti-CD22 CAR-T Preclinical in vivo Assay

Schematic representation of the CD22 and B-cell receptor signaling process
March 2013

Anti-CD22 CAR-T Cell Therapy

Results from a preclinical test that investigated how different structural modifications and alterations of CD22-specific CARs in targeting epitopes, signaling domains and spacer length affect the efficacy of CAR-T cells showed that CARs targeting a proximal CD22 domain had stronger antitumor activity than those binding other epitopes. Interestingly, modifications on other structural components of anti-CD22 CARs have no significant influence on the efficacy. In addition, the CAR-expressing T cells improved survival of ALL xenograft models. Recently, several anti-CD22 CAR have entered clinical evaluation in patients with recurrent, chemotherapy resistant or refractory ALL. Patients with CD19-refractory or resistant lymphoma have also been involved in one trial.

Animal Models for in vivo Study of anti-CD22 CAR-T Cell Therapy

We have successfully developed various animal models for the preclinical in vivo assay of anti-CD22 CAR-T cell therapy. Immunodeficiency mice are delivered intravenously, subcutaneously, or intraperitoneally with different kinds of CD22+ cells such as lymphoma cell lines (NALM-6), CD22 transfected cell lines, human primary lymphoma cells, and customized cell lines to set up murine B-cell malignancy models. We also offer non-human primate (NHP) and rat models at your requests.

In vivo Assay Parameters and Techniques

At Creative Biolabs, we offer the most exquisite and comprehensive service platform for anti-CD22 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 in vivo assessments of CAR-T are essential for its construct optimization, risk managements, and dosage determination. With years of experience in developing CAR-T therapy solutions, Creative Biolabs offers a broad range of services to support your research on anti-CD22 CAR-T therapy development.

References

  1. Sullivan-Chang, et al. "Targeting CD22 in B-cell malignancies: current status and clinical outlook."BioDrugs 27.4 (2013): 293-304.
  2. Long, et al. "Lessons learned from a highly-active CD22-specific chimeric antigen receptor. Oncoimmunology 2013; 2: e23621; PMID: 23734316.
  3. Haso, et al. "Anti-CD22–chimeric antigen receptors targeting B-cell precursor acute lymphoblastic leukemia." Blood 121.7 (2013): 1165-1174.

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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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