Dr Claire Huguet of Randox Biosciences explains how precise antibody selection is enabling companion diagnostics (CDx) to drive the development of personalised medicine.
Companion diagnostics (CDx) represent a major step forward in the development of precision medicine. These enable a novel drug to be prescribed only to the patients expressing a marker of interest in relation to the drug mechanism. Due to their primary use in oncology, the focus so far has been on molecular and tissue-based assays. However, with personalised medicine principles extending to therapeutic areas beyond cancer treatment, and with the realisation of the potential of liquid biopsies, the interest for antibody-based CDx is growing fast.
What will make the next CDx immunoassays successful, then, with so many assays already available and the race to generate the antibodies against novel targets accelerating in the market?
Intimate knowledge of the disease's biology has proved crucial to developing novel therapeutic molecules, and in-depth understanding of the best antibody target will permit the CDx immunoassays of the future to define the patient population eligible for a given treatment.
The journey starts at the immunisation level, engineering the most appropriate hapten to favour an antibody response of the highest specificity for the molecular target. Ideally, the latter must be robust enough to ensure good marker stability in patient samples.
This means understanding the degradation pathways that will affect the target in the bloodstream, within the body and at pre-analytical stages.
It should also be highly preserved between species, so that the same antibody raised against a human protein target can show high cross-reactivity for the same target in animal samples, avoiding the need for antibody remake, and relating bridging studies, between pre-clinical and clinical assessment of the candidate biomarker. This also means avoiding the risk of being unable to reproduce in the clinic the signal that was observed in the early stages of the drug development.
The molecular target for the antibody should also take into account the various biological entities that may interfere in the anitibody binding and generate inaccurate signals - with a clear understanding that consequences for the patient may have to include assessing whether or not they receive a life-critical medication.
Selecting highly repeated motifs can help increase the assay sensitivity, while the need to target hardly accessible epitopes will benefit from experience with antibody fragment technology.
Certainly, the final antibody selection and the quality of the assay development stages will also affect the ultimate performance of the immunoassay released for testing. However, it is the molecular targeting steps, and the ability to selectively elicit the appropriate antibody specificity, that will make a difference in the appropriateness of the assay to be raised as a CDx.
Selective hapten engineering and custom antibody development have been among Randox Biosciences' strengths for many years, and it is proud contribute to personalised medicine strategies as they unfold.