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Anti-VEGFR2 CAR-T Preclinical in vivo Assay

Target Background

Vascular endothelial growth factor receptor type2 (VEGFR2) is a receptor tyrosine kinase (RTK) overexpressed in a variety of cancer cells especially in metastatic cancer cells such as melanoma and renal cancer. It belongs to the VEGFR superfamily and plays important roles in tumor cell proliferation, survival, invasion and tumor angiogenesis owing to high dependency of tumor cells on the tumor vasculature. VEGF antibodies that block the access to its ligand exert inhibitory effects against angiogenesis in contrast to the modest anti-tumor effects. The preclinical study of redirection of mouse T cells to murine VEGFR2 by CAR significantly inhibit the growth of subcutaneously implanted CT26 adenocarcinoma and B16.F10 melanoma without acute toxicity, and thus advances anti-VEGFR2 CAR-T therapy to Phase I/II clinical trials.

Anti-VEGFR2 CAR-T Preclinical in vivo Assay

Anti-VEGFR2 CAR-T Cell Therapy

Many preclinical studies have demonstrated positive response of anti-VEGFR2 CAR-T in mouse syngeneic colon adenocarcinoma and melanoma models as well as xenograft transplants of human colon adenocarcinoma. A humanized VEGFR-2 CAR derived from the antibody KDR1121 has been employed in a Phase I/II trial for metastatic cancers. Toxicities, such as cytokine-induced hypotension, are dose-related and can be avoided when administered with purified CD8+ T cells. However insufficient anti-tumor effects caused by lower-dosage CAR-T cells require that more investigations in the optimization of CAR-T cells and more tests in the preclinical stage need to be conducted.

Animal Models for in vivo Study of anti-VEGFR2 CAR-T Cell Therapy

Creative Biolabs provides customers with versatile animal models for anti-VEGFR2 CAR T in vivo assay that includes but not limited to the following categories.
Vascularized syngeneic mouse models for melanoma, colon adenocarcinoma, fibrosarcoma, renal adenocarcin. Usually 6 to 8-week old C57BL/6 mice are adopted for the subcutaneously inoculation of syngeneic tumor cells. Treatment with anti-VEGFR2 CAR-T cells concomitantly with i.p. injection of rhIL-2 is initiated when tumor volume reaches 30-80 mm2 after a nonmyloablative lymohopemia. Subsequent procedures including in vivo T cell persistence evaluation, tumor volume record, clinical observation, disease remission & survival and other required endpoints will be evaluated.
Xenograft mouse models for metastatic cancers. Creative Biolabs also assist customers in efficacy tests of anti-VEGFR2 CAR-T cells targeting human breast cancer, Non small-cell lung cancer (NSCLC), pancreatic cancer, and disseminated leukemic cancers. Our professional team and all-around service platforms will greatly promote the development of your studies.

In vivo Assay Parameters and Techniques

At Creative Biolabs, we offer the most exquisite and comprehensive service platform for anti-VEGFR2 CAR-T cell therapy research.
Efficacy Test
Tumor remission monitored by bioluminescence imaging (BLI)
Survival curve tracking
Immuofluorescent microscopy
Viability and Bio-distribution Studies
Tumor infiltration, 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)
Cytokine storm surveillance (fever, hypertension, prolonged cytopenia)
Complete necropsy/organ weight
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.

Progressing with the technology of CAR development and focused on the evaluation of CAR-T efficacy, Creative Biolabs continuously expands the service portfolio in in vivo tests, aiming to bridge the gap between early development and the final application of CAR-T cell therapy.

References

  1. 1. Chinnasamy, et al. "Gene therapy using genetically modified lymphocytes targeting VEGFR-2 inhibits the growth of vascularized syngenic tumors in mice." The Journal of clinical investigation 120.11 (2010): 3953-3968.

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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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