Capturing TCR from cfDNA
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4.9 years ago
CY ▴ 740

I recently came across a poster (unfortunately it is confidential) that capture TCR from cfDNA in patient with solid tumor.

I got confused regarding the difference between capturing TCR from cfDNA and typical TCR-Seq of PBMC (peripheral blood). Does the former method yield any advantage? perhaps there is some biological differences in this (something like that TCRs captured from cfDNA are enriched from T-cells died interacting with tumor?)?

Can anyone having experience on this share some comments? Thanks in advance.

TCR cfDNA ctDNA • 1.2k views
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Yes, the idea would be [I presume] that a proportion of the cfDNA will represent circulating tumour DNA (ctDNA); thus, profiling the t-cell receptors in this may be a proxy for detecting it in the tumour. The assumption could be that the TCR in the ctDNA has picked up a somatic mutation.

It would also be very interesting to capture circulating tumour cells (CTCs) and perform the same profiling on these. ctDNA may just be from cells that have necrosed, whereas CTCs are cells that have actually liberated themselves from the tumour bulk.

The overarching idea, then, may be to develop a personalised immunotherpy approach based on the t-cell receptors. This all may then also tie-in with TILs, tumour infiltrating lymphocytes, which are predictive of response, as far as I know.

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