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Our pan-Trk antibody is used in an in vitro diagnostic to identify cancer patients suitable for Larotrechtinib treatment.
Not all prescribed drugs work equally for each individual. Many factors affect the efficacy of a drug including the patient's genetics, their lifestyle choices, or even their gender and ethnicity can have a significant impact on treatment outcome. Precision medicine aims to reduce these biases by using optimized diagnostic testing to assess a patient’s genetic background allowing clinicians to select the most appropriate treatment. However, the field of precision medicine can only move forward if the appropriate diagnostic tests are available and approved for use.
The first in vitro diagnostic (IVD) for detecting variations in Trk receptors (a family of tyrosine kinases) is now approved for use across multiple solid tumor types. The VENTANA pan-TRK (EPR17341) immunohistochemistry assay is the first of its kind to detect wild-type and chimeric fusion proteins occurring in the Trk C-terminal region. These fusion proteins occur after chromosomal rearrangements of the TRK gene to form neurotrophic tyrosine kinase (NTRK) receptors, an oncogenic driver responsible for the formation of many different tumor types.
We developed the Trk antibody that provides high specificity within Ventana’s companion diagnostic. The antibody is designed to recognize a short region within the C-terminal domain conserved across all three of the wild-type TRK proteins, A, B, and C. Conservation across proteins and the specific binding capability of the antibody allows for the diagnostic to act as a pan-Trk test recognizing fusion proteins created by any of the three TRK variants. We have also developed Anti-Pan Trk antibody [EPR17341] (ab181560), a research use only (RUO) antibody of the clone used in the VENTANA pan-TRK (EPR17341) immunohistochemistry assay.
Our TRK antibody used in the IVD was developed using recombinant technology. Recombinant antibodies are generated using synthetically derived immunogens making their production consistent and ensuring batch-to-batch reproducibility. These traits make the antibody ideal for use in companion diagnostics, and they allow clinicians to generate consistent and reproducible results between every diagnostic test they run.
We have developed several other recombinant rabbit monoclonal antibody clones against Trk:
The progression of precision medicine technologies such as IVDs has the potential to help thousands of lives including those who have very rare and previously untreatable cancers. In some rare tumors, including infantile fibrosarcoma and secretory breast carcinoma, Trk fusion proteins are the defining genetic feature in around 90% of cases1. There are also some commonly occurring tumors containing TRK-fusion proteins, including lung, thyroid, and sarcoma however here they occur at a much lower frequency at <1%1.
The future is now looking more hopeful for patients suffering from these cancers. The FDA has approved the use of the drug Larotrechtinib for treatment of solid tumors containing TRK-fusion proteins. So far Larotrechtinib treated patients have shown a 75% response rate in clinical trials compared to 20-30% from traditional chemotherapies. The availability of this IVD test to identify patients suitable for Larotrechtinib treatment is a huge leap forward for precision medicine. The use of antibody-based technology for this diagnostic test is much cheaper and faster than using gene-sequencing approaches, enabling the acceleration of precision medicine techniques in the clinic.
1) Cocco, E., Scaltriti, M., & Drilon, A. (n.d.). NTRK fusion-positive cancers and TRK inhibitor therapy. Nature Reviews Clinical Oncology. https://doi.org/10.1038/s41571-018-0113-0