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Anti-CD30 CAR-T Preclinical in vivo Assay

Target Background

CD30 antigen, also known as TNFRSF8, is a trans-membrane glycoprotein of the tumor necrosis factor receptor (TNFR) superfamily. Normally CD30 is restricted to activated B and T lymphocytes while rarely expressed by resting counterparts. CD30 has pleiotropic effects on the growth and survival of cells involving NF-κB signaling pathway. It is associated with almost all Hodgkin lymphoma (HL) and some subtypes of non-Hodgkin lymphoma (NHL) such as anaplastic large cell lymphoma (ALCL) at diagnosis as well as relapse. Therefore, CD30 is a very attractive target for the immunotherapy of these diseases. Brentuximab vedotin (Adcetris, Seattle Genetics), approved by FDA in 2011 for relapsed or refractory HL and systemic ALCL, is an antibody-drug conjugate (ADC) directed to CD30. Anti-CD30 CAR-T cell therapies are also being developed in many institutes and companies.

Anti-CD30 CAR-T Preclinical in vivo Assay

The Immune System, Inflammation, and Cancer

Anti-CD30 CAR-T Cell Therapy

Several clinical trials have been initiated for anti-CD30 CAR-T therapy. Patients with relapsed or refractory CD30+ HL or NHL are recruited. In a Phase I trial, nine patients were treated with autologous anti-CD30 CAR EBV-specific cytotoxic T-lymphocytes (CTLs). The CTLs were involved due to their long persistence in the blood stream for many years, potentially induces a prolonged anti-tumor effect. The anti-CD30 CAR-CTLs produced no adverse events, however, only two patients had a complete or partial response. Meanwhile, a novel 4th generation anti-CD30 CAR incorporated with an inducible caspase 9 suicide gene is being evaluated for both efficacy and safety.

Animal Models for in vivo Study of anti-CD30 CAR-T Cell Therapy
We have developed multiple animal models for the preclinical in vivo assay of anti-30 CAR-T cells. Several kinds of CD30+ cell lines or human primary HL and NHL cells, and some CD30 transfected cell lines are injected subcutaneously, intraperitoneally, or intravenously in SCID mice to create tumors in the mice. We also provide rats and non-human primates (NHPs) models to meet your special requirements.

In vivo Assay Parameters and Techniques

At Creative Biolabs, we offer the most exquisite and comprehensive service platform for anti-CD30 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 cells are essential for their construct optimization, risk managements, and dosage determination. As a global leader in life sciences, Creative Biolabs offers a broad range of standardized and customized preclinical in vivo assay services for clients of Pharma & Biotech or other life sciences organizations. Our expertise covers many aspects of CAR-T in vivo evaluation. A variety of reliable rodent models and assay systems, as well asmodels of other species including NHP, are available.

References

  1. Hombach, et al. "T cells engrafted with a recombinant anti-CD 30 receptor target autologous CD 30+ cutaneous lymphoma cells." Gene therapy 8.11 (2001): 891-895.
  2. Savoldo, et al. "Epstein Barr virus–specific cytotoxic T lymphocytes expressing the anti-CD30ζ artificial chimeric T-cell receptor for immunotherapy of Hodgkin disease." Blood 110.7 (2007): 2620-2630.
  3. Di Stasi, et al. "T lymphocytes coexpressing CCR4 and a chimeric antigen receptor targeting CD30 have improved homing and antitumor activity in a Hodgkin tumor model." Blood 113.25 (2009): 6392-6402.

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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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