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Anti-MART-1 TCR-T Preclinical in vivo Assay

Target Background

Melanoma Antigen Recognized by T cells 1 (MART-1) is a protein antigen encoded by the MLANA gene and found on the surface of melanocytes and the vast majority (80%) of melanomas. MART-1 is presented by MHC class I complexes to T cells of the immune system. The specific expression profile of MART-1 antigen in melanocyte lineage makes it a marker for melanocytic tumors. Of note, careful attention needs to be paid when targeting this antigen due to the fact that MART-1 antigen is also found in benign nevi as well.

Anti-MART-1 TCR-T Preclinical in vivo Assay

Anti-MART-1 TCR-T Cell Therapy

A series of clinical trials of TCR-T cell therapy targeting melanoma have been conducted since 2006. From the earlier modification of T cells with MART-1 specific T-cell receptor (DMF4) that shows limited response (2/17) to the latest trial in which MART-1 reactive TCR-T cell therapy is combined with a peptide pulsed DC vaccine, efforts to explore the optimization strategies have never been indulged. Nevertheless, toxicities such as erythematous skin rash, anterior uveitis, and hearing loss are observed due to the on-target recognition of the MART-1 antigen. Further studies aiming at avoiding these unwanted effects have to be conducted prior to clinical trials.

Animal Models for in vivo Study of anti-MART1 TCR-T Cell Therapy

Xenograft models for metastatic melanoma are available at Creative Biolabs. Firefly luciferase-labeled human melanoma cells Mel 624 are intravenously injected into the NSG mice. Adoptive CD8/MART-1/TCR+ T cell are given when tumor sizes reach certain criteria according to the BLI observation. Close disease monitoring are proceeded regularly and euthanasia are executed when moribund appears. In addition, Creative Biolabs provides CD34+ humanized mice that are better for the in vivo evaluation of TCR-T cell therapy.

Xenograft models for subcutaneously transplanted melanoma are established by subcutaneously injecting human melanoma cells (Mel 624 or other MART-1 positive cells) into the left flank of NSG or HHDxRag-/- mice. Antitumor effects are regularly evaluated by measuring tumor mass using fine calipers. Anti-MART1 TCR-T cells are given when palpable tumors develop via intravenously injection. Creative Biolabs provides strict observations and other endpoint procedures based on the specific requirements. Mice are subjected to euthanasia when either tumor reaches the maximum permitted size or moribund appears.

In vivo Assay Parameters and Techniques

At Creative Biolabs, we offer the most exquisite and comprehensive service platform for preclinical anti-MART1 TCR-T cell therapy research.
Efficacy Test
Tumor remission monitored by bioluminescence imaging (BLI)
FACS analysis
Survival curve tracking
Immuofluorescent microscopy
Immunohistochemistry
Viability and Bio-distribution Studies
Tumor infiltration, TCR-T cell durability, GLP-compliant bio-distribution studies
Cytokine release analysis (analysis of the pre- and post-infusion plasma samples)
Toxicity Evaluation
Pilot tolerability (MTD, the route of administration, dose regimen / response / onset)
Clinical observation (body weight, behavior, feed consumption)
Complete blood counts (CBC) and serum chemistry
Complete necropsy/organ weight
Histopathological analysis
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.

Creative Biolabs consistently keeps track of the most up-to-date in vivo study techniques around the world in order to meet the increasingly rigorous need for CAR-T/TCR-T cell therapy development. We renew and replenish our techniques and services timely and regularly. Please feel free to contact us for more information.

References

  1. Hu, et al. "Human melanoma immunotherapy using tumor antigen-specific T cells generated in humanized mice." Oncotarget 7.6 (2016): 6448.
  2. Leisegang, et al. "Targeting human melanoma neoantigens by T cell receptor gene therapy." The Journal of clinical investigation 126.3 (2016): 854.

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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:

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Tel: 44-207-097-1828

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