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Durable complete response in a patient with metastatic melanoma following adoptive transfer of autologous T cells recognizing 10 mutated tumor antigens
  1. Todd D Prickett1,
  2. Jessica S Crystal2,
  3. Jared J Gartner1,
  4. Yao Xin1,
  5. Pasetto Anna3,
  6. Alena Gros1,
  7. Yong-Chen Lu3,
  8. Yong Li1,
  9. Mona El-Gamil1,
  10. Steven A Rosenberg3 and
  11. Paul Robbins1
  1. Aff1 grid.94365.3d0000000122975165National Cancer InstituteNational Institutes of Health Bethesda MD USA
  2. Aff2 grid.430387.b0000000419368796National Cancer InstituteNational Institutes of Health, Rutgers Robert Wood Johnson Medical School New Brunswick NJ USA
  3. Aff3 grid.48336.3a0000000419368075Surgery BranchNational Cancer Institute, National Institutes of Health Bethesda MD USA

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Meeting abstracts

Durable complete response rates of 20% have been observed in clinical trials of patients with metastatic melanoma employing adoptive cell transfer (ACT) of patient derived tumor infiltrating lymphocytes (TIL). Here we provide a detailed analysis of the response of TIL administered to a patient with metastatic melanoma who exhibited a complete response ongoing greater than 3 years. Using whole exome and RNA sequencing and bioinformatic analysis of the patient's matched tumor and normal gDNA we identified over 4,000 non-synonymous somatic mutation variants. We screened 745 somatically mutated genes using tandem minigene constructs expressing transcripts expressed in autologous tumor cells whose expression levels were greater than 0.1% of the levels of β- actin. These tandem minigenes were then transfected into autologous B cells and then analyzed for their ability to stimulate the administered T cells. Our results indicated that the autologous TIL distinctly recognized 10 somatically mutated gene products, each of which was recognized in the context of three different HLA class I restriction elements expressed by the patient's tumor. Detailed T cell clonal analysis revealed that 9 of the top 20 most prevalent clones present in the infused TIL, comprised over ¼ of total infused cells and recognized mutated antigens. These results further supported our efforts to identify and enrich mutation-reactive T cells for the treatment of patients with metastatic cancer.