Background Adoptive transfer of T-cell receptor-engineered T cells (TCR-T cells) has shown promising efficacy in solid tumor treatment, but achieving clinical benefit typically requires infusion of tens of billions of cells. The commonly used rapid expansion protocol (REP), based on the CD3-agonistic OKT3 antibody and irradiated allogeneic feeder cells, exponentially expands tumor-infiltrating lymphocytes (TILs). However, the effect of REP on TCR-T cell frequency and phenotype remains unclear. This study aimed to …

<title>Abstract</title> Adoptive cell transfer (ACT) using neoantigen reactive T lymphocytes can mediate cancer regression. Here, we developed methods to isolate unique, personalized, neoantigen reactive T cell receptors (TCRs) from tumor infiltrating lymphocytes (TIL) from patients with metastatic gastrointestinal cancers and incorporate the TCR α and β chains into gamma retroviral vectors. We transduced autologous peripheral blood lymphocytes (PBL) using γ-retroviruses and adoptively transferred those cells into…

Background Cellular immunotherapies using autologous tumor-infiltrating lymphocytes (TIL) can induce durable regression of epithelial cancers in selected patients with treatment-refractory metastatic disease. As the genetic engineering of T cells with tumor-reactive T-cell receptors (TCRs) comes to the forefront of clinical investigation, the rapid, scalable, and cost-effective detection of patient-specific neoantigen-reactive TIL remains a top priority. Methods We analyzed the single-cell transcriptomic states of…

&lt;div&gt;AbstractPurpose:&lt;p&gt;Immune checkpoint blockade (ICB) agents and adoptive cell transfer (ACT) of tumor-infiltrating lymphocytes (TIL) are prominent immunotherapies used for the treatment of advanced melanoma. Both therapies rely on activation of lymphocytes that target shared tumor antigens or neoantigens. Recent analysis of patients with metastatic melanoma who underwent treatment with TIL ACT at the NCI demonstrated decreased responses in patients previously treated with anti–PD-1 agents. We aimed…

&lt;p&gt;Supplemental Figure S3. Surface phenotype of Akti-treated and vehicle TIL isolated from patient with melanoma and expanded to clinical scale for 30 days prior to adoptive-transfer into humanized mouse model.&lt;/p&gt;