Advance in immune cell screening uncovers receptors that target prostate cancer

Good news! Cancer is history (soon)! May the next generation of humans know cancer only from annals of history! 😊

"... The researchers discovered three previously unidentified, naturally occurring T-cell receptors that target prostate cancer using their screening method. In validation tests, T-cell receptors associated with the highest levels of secretion were the most likely to elicit a response against cancer cells. Rate of functional T-cell receptors was around tenfold higher than using previous techniques. ..."

From the significance and abstract (strangely, the abstract does not mention the prostrate cancer related part of their research even though it is part of the study):

"Significance

T cells possess a vast diversity of surface receptors that bind to antigens presented on target cells, resulting in the activation of functions such as secretion of cytokines or cytotoxic molecules. T cell receptor (TCR) immunotherapies leverage this system to target tumor cells for elimination, yet methods of identifying rare TCRs remain nonspecific, resulting in many nonfunctional TCRs. We apply microcavity-containing hydrogel microparticles, known as nanovials, to selectively bind to and activate target T cells and capture secreted cytokines. This method enabled the linkage of TCR binding and functional secretion of cytokines directly with TCR sequences at the single-cell level, leading to expanded repertoires of TCRs and reduced false positives, ultimately enhancing the prospects of T cell cancer immunotherapy.

Abstract

The ability to selectively bind to antigenic peptides and secrete effector molecules can define rare and low-affinity populations of cells with therapeutic potential in emerging T cell receptor (TCR) immunotherapies. We leverage cavity-containing hydrogel microparticles, called nanovials, each coated with peptide-major histocompatibility complex (pMHC) monomers to isolate antigen-reactive T cells. T cells are captured and activated by pMHCs inducing the secretion of effector molecules including IFN-γ and granzyme B that are accumulated on nanovials, allowing sorting based on both binding and function. The TCRs of sorted cells on nanovials are sequenced, recovering paired αβ-chains using microfluidic emulsion-based single-cell sequencing. By labeling nanovials having different pMHCs with unique oligonucleotide-barcodes and secretions with oligo-barcoded detection antibodies, we could accurately link TCR sequences to specific targets and rank each TCR based on the corresponding cell’s secretion level. Using the technique, we identified an expanded repertoire of functional TCRs targeting viral antigens with high specificity and found rare TCRs with activity against cancer-specific splicing-enhanced epitopes."

Advance in immune cell screening uncovers receptors that target prostate cancer | UCLA

Defining T cell receptor repertoires using nanovial-based binding and functional screening (open access)

Fig. 1 Overview of high-throughput analysis and isolation of antigen-specific T cells followed by recovery of a single-cell TCR library.

Fig. 5 Multiplexed secretion-based profiling of prostate tissue antigen-specific T cells.