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Anti-CD38 CAR-T Preclinical in vivo Assay

Target Background

CD38 or ADPRC1 (cyclic ADP-ribose hydrolase) is a multifunctional ectoenzyme located on the surface of several kinds of immune cells (CD4+, CD8+, B lymphocytes and natural killer cells) and functions for hydrolysis of cyclic ADP-ribose (cADPR) from NAD+ to ADP-ribose, then regulates cytoplasmic Ca2+ flux. It is uniformly overexpressed in a variety of haematological malignancies such as chronic lymphocytic leukemia (CLL), multiple myeloma, acute promyelocytic leukemia (PML), B-cell non-Hodgkin lymphoma (NHL), B-cell acute lymphoblastic leukemia (ALL), B-cell chronic lymphocytic leukemia (B-CLL), T-cell ALL and solid tumors such as nasopharyngeal carcinoma, compared to normal lymphoid and myeloid cells. Meanwhile, the expression of CD38 is a marker of poor prognosis in CLL. All these characteristics make CD38 a potential target and unceasingly attract growing interest for anti-CLL therapy.

The multiple enzymatic reactions catalyzed by CD38

The multiple enzymatic reactions catalyzed by CD38
Physiological reviews 88.3 (2008): 841-886

Anti-CD38 CAR-T Cell Therapy

Accumulative preclinical studies proved the target-cell killing of multiple CD38-overexpressed myeloma cells induced by several anti-CD38 monoclonal antibodies or antibody-drug conjugates such as Daratumumab (HuMax-CD38, Genmab), which led to multiple currently recruiting and ongoing phase 1–2 studies (NCT02336815; NCT01421186; NCT02419118; NCT01998971; NCT00574288, etc.). For instance, a phase 1/2 study (NCT01084252) has been authorized to recruit patients for dose escalation and efficacy test of anti-CD38 monoclonal antibody in patients with selected CD38+ hematological malignancies. These studies will lay the sufficient foundation and offer researchers a great chance of initiating the first anti-CD38 CAR-T study since no clinical trial of anti-CD38 CAR-T has been reported up to now, even pre-clinical experiment. Creative Biolabs will help you open up the first road to anti-CD38 CAR-T cell therapy in the scientific community.

Animal Models for in vivo Study of anti-CD38 CAR-T Cell Therapy

Creative Biolabs provides versatile animal models for a variety of haematological malignancies such as chronic lymphocytic leukemia (CLL), multiple myeloma, acute promyelocytic leukemia (PML), B-cell non-Hodgkin lymphoma (NHL), B-cell acute lymphoblastic leukemia (ALL), B-cell chronic lymphocytic leukemia (B-CLL), T-cell ALL and solid tumors such as nasopharyngeal carcinoma. Take B-cell lymphoma as an example, the following figure shows the related murine models Creative Biolabs provided.

CD38

In addition, Creative Biolabs also assists customers in creating clinically relevant orthotopic mouse models including but not limited to the above categories.

In vivo Assay Parameters and Techniques

At Creative Biolabs, we offer the most exquisite and comprehensive service platform for preclinical anti-CD38 CAT-T cell therapy research.
Efficacy Test
Tumor remission monitored by tumor volume recording 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

To occupy the virgin land of CAR-T cell therapy, Creative Biolabs provides researchers with the most reliable and relevant animal models for better and the most scientific preclinical studies. Furthermore, we offer customized service and help design and perfect study strategies for the top-ranking research.
Please feel free to contact our customer service for more information.

References

  1. Mohammed, Sally Elsir, et al. "The retinoid derivative drug, acitretin, modulates CD38 expression on MEC-1 cells and primary chronic lymphocytic leukemia (CLL) cells and reduces migration in response to the chemokine CXCL12." Blood 126.23 (2015): 5271-5271.
  2. Donnou, Sabrina, et al. "Murine models of B-cell lymphomas: promising tools for designing cancer therapies." Advances in hematology 2012 (2012).
  3. Malavasi, Fabio, et al. "Evolution and function of the ADP ribosyl cyclase/CD38 gene family in physiology and pathology." Physiological reviews 88.3 (2008): 841-886.

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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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