Tissue Cross Reactivity (TCR) Assay Service for CAR-T Cell Pre-clinical Characterization

All products and services are For Research Use Only and CANNOT be used in the treatment or diagnosis of disease.

The use of CAR-T cells has been demonstrated to be a promising treatment against hematological malignancies with successes in the autologous setting. Despite the encouraging results achieved in the clinical setting, tumorigenicity and off-target toxicity are still the main concerns of its clinical application. The non-specific activation of patient T cells not only induces cytotoxic activity against tumors, but also induces harmful toxicity against normal tissues, leading to immune-related adverse events. Therefore, to perform T cell therapy safely and effectively, immunotherapy using T cells that can accurately separate tumor cells from normal cells is required.

To clarify the characteristics of antitumor CAR more precisely for expansion of treatment modalities, Creative Biolabs provides cross tissue reactivity study services to help customers investigate the potential target-specific reactivity of CAR-redirected T cells in vitro and in vivo.

Typical TCR Study Plan

Phase 1: Initial analysis and protocol optimization

For the rest of the plan, this stage is the most critical and important. At Creative Biolabs, we are most concerned about the development of the initial protocol to ensure the smooth progress of the subsequent GLP phase. If feasible, the method will be developed on an automated platform, if not, the method will be developed manually. Method development will be completely driven by science and data.

Our assay development complies with the most recent guidelines on analytical validation. Our fit-for-purpose validation is very strict, allowing us to inform you promptly on the outcome of the method validation progress in time. You will immediately be notified of the most critical verification parameters to quickly help you with the next steps.

Phase 2: Optional - preliminary TCR screen

To improve the staining conditions (matrix effect) of various tissues, especially the preliminary assessment of background staining in different tissue types, and the preliminary assessment of possible targets or target staining, a non-GLP screening phase may be conducted. This may also be useful for the preparation of the final GLP study.

The common format of this method is twelve tissues from two different donors. TMA (tissue micro array) format can also be used to screen all tissues required by FDA and EMA, especially for first-class biopharmaceuticals. Here, before conducting in vivo safety (toxicology) studies, model animal species can be screened after verifying cross-species reactivity.

The list of 33 tissues recommended by the FDA and screened as part of this study:

Adrenal
Bladder
Blood cells
Bone marrow
Breast
Cerebellum
Cerebral Cortex
Colon
Endothelium
Eye
Fallopian tube

Gastrointestinal tract
Heart
Kidney, medulla & cortex
Liver
Lung
Lymph node
Ovary
Pancreas
Parathyroid
Pituitary
Placenta

Prostate
Skeletal muscle
Skin
Spinal cord
Spleen
Testis
Thymus
Thyroid
Ureter
Uterus, endometrium
Uterus, cervix

Phase 3: Comprehensive TCR screen

In the third stage, in accordance with the requirements of the FDA and EMA, the main GLP study was conducted on 38 panels of human tissues/organs from at least three unrelated, unaffected donors.

If automatic methods are used, the turnaround time for these studies (including the reporting phase) is 2 months, and if manual methods are used, it is 3 months. The data is entered into an Excel file, printed, dated, and signed. Our quality check will ensure the integrity of the data, and our report will contain visibly stained images.

The Applications of Tissue Cross-Reactivity

There are many applications for TCR analysis. They include:

Determine the patient's potential risk
Compile a complete tissue library of various species including species, including infected tumors and tissues, fixed or frozen tissues, and in vivo studies
Generate high-quality audit reports
Digital microscope
Quality assurance
Critical stage review
Efficient reporting and planning
Prepare research-specific solutions for specific needs

Highlights of Our TCR Service

Tissue Cross Reactivity (TCR) Assay Service for CAR-T Cell Pre-clinical Characterization

Our cross-reactivity assays follow the FDA and EMEA guidelines :

33 or 36 complete organ parts recommended by the guide
3 unrelated human donors to screen for polymorphisms
Assay on frozen adult tissue
Positive and negative controls are critical to the interpretation of results, and they confirm the reliability of the measurement.
Assay under GLP conditions

For more detailed information about our technology platform for TCR assay, please visit:

Surfarray™ Cell Microarray Technology

Please feel free to contact us or directly sent us an inquiry.