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Full-Text Articles in Medicine and Health Sciences

Single Cell Sequencing To Identify Tcrs That Recognize Autologous Tumor Cells After Vaccination With Allogeinic Dribble Vaccine, Hong-Ming Hu, Christopher C. Paustian, Zhifa Wen, Tarsem L. Moudgil, Traci L. Hilton, Sam Bookhardt, Guangjie Yu, Eric Tran, Venkatesh Rajamanickam, Walter Urba, Rachel E. Sanborn, Bernard A. Fox Mar 2019

Single Cell Sequencing To Identify Tcrs That Recognize Autologous Tumor Cells After Vaccination With Allogeinic Dribble Vaccine, Hong-Ming Hu, Christopher C. Paustian, Zhifa Wen, Tarsem L. Moudgil, Traci L. Hilton, Sam Bookhardt, Guangjie Yu, Eric Tran, Venkatesh Rajamanickam, Walter Urba, Rachel E. Sanborn, Bernard A. Fox

Eric Tran, PhD

Background: Adoptive immunotherapy with tumor-specific TCR gene-modified T cells has the potential to eradicate bulky disease. Traditional methods of TCR identification require lengthy in vitro culture to generate clonal T-cell populations, which adds time and complexity to this promising therapy. Here we described a simplified and reliable method to identify TCRs by single cell TCR sequencing of cells sorted with antibodies against T-cell surface markers that are up-regulated only when they are stimulated with specific tumor cell antigens.

Methods: A tumor-infiltrating lymphocyte (TIL) culture with T cells reactive against autologous tumor was generated from a brain metastasis of a patients …


Enhanced Detection Of Neoantigen-Reactive T Cells Targeting Unique And Shared Oncogenes For Personalized Cancer Immunotherapy., Rami Yossef, Eric Tran, Drew C Deniger, Alena Gros, Anna Pasetto, Maria R Parkhurst, Jared J Gartner, Todd D Prickett, Gal Cafri, Paul F Robbins, Steven A Rosenberg Mar 2019

Enhanced Detection Of Neoantigen-Reactive T Cells Targeting Unique And Shared Oncogenes For Personalized Cancer Immunotherapy., Rami Yossef, Eric Tran, Drew C Deniger, Alena Gros, Anna Pasetto, Maria R Parkhurst, Jared J Gartner, Todd D Prickett, Gal Cafri, Paul F Robbins, Steven A Rosenberg

Eric Tran, PhD

Adoptive cell transfer (ACT) of tumor-infiltrating lymphocytes (TILs) targeting neoantigens can mediate tumor regression in selected patients with metastatic epithelial cancer. However, effectively identifying and harnessing neoantigen-reactive T cells for patient treatment remains a challenge and it is unknown whether current methods to detect neoantigen-reactive T cells are missing potentially clinically relevant neoantigen reactivities. We thus investigated whether the detection of neoantigen-reactive TILs could be enhanced by enriching T cells that express PD-1 and/or T cell activation markers followed by microwell culturing to avoid overgrowth of nonreactive T cells. In 6 patients with metastatic epithelial cancer, this method led to …