<p class="first" id="d1390201e216">The adoptive transfer of neoantigen-reactive tumor-infiltrating
lymphocytes (TILs)
can result in tumor regression in patients with metastatic cancer. To improve the
efficacy of adoptive T cell therapy targeting these tumor-specific mutations, we have
proposed a new therapeutic strategy, which involves the genetic modification of autologous
T cells with neoantigen-specific T cell receptors (TCRs) and the transfer of these
modified T cells back to cancer patients. However, the current techniques to isolate
neoantigen-specific TCRs are labor intensive, time consuming, and technically challenging,
not suitable for clinical applications. To facilitate this process, a new approach
was developed, which included the co-culture of TILs with tandem minigene (TMG)-transfected
or peptide-pulsed autologous antigen-presenting cells (APCs) and the single-cell RNA
sequencing (RNA-seq) analysis of T cells to identify paired TCR sequences associated
with cells expressing high levels of interferon-γ (IFN-γ) and interleukin-2 (IL-2).
Following this new approach, multiple TCRs were identified, synthesized, cloned into
a retroviral vector, and then transduced into donor T cells. These transduced T cells
were shown to specifically recognize the neoantigens presented by autologous APCs.
In conclusion, this approach provides an efficient procedure to isolate neoantigen-specific
TCRs for clinical applications, as well as for basic and translational research.
</p><p class="first" id="d1390201e220">The identification of antigen-specific T cell
receptors (TCRs) is a complicated process,
which is technically challenging and not suitable for clinical applications. To simplify
this process, Lu and colleagues developed an efficient single-cell approach, which
can significantly reduce the labor and time for the TCR isolation.
</p>