title: Generation of Induced Pluripotent Stem Cells from Human Melanoma Tumor-infiltrating Lymphocytes.
abstract: Adoptive transfer of ex vivo expanded autologous tumor-infiltrating lymphocytes (TILs) can mediate durable and complete responses in significant subsets of patients with metastatic melanoma. Major obstacles of this approach are the reduced viability of transferred T cells, caused by telomere shortening, and the limited number of TILs obtained from patients. Less-differentiated T cells with long telomeres would be an ideal T cell subset for adoptive T cell therapy;however, generating large numbers of these less-differentiated T cells is problematic. This limitation of adoptive T cell therapy can be theoretically overcome by using induced pluripotent stem cells (iPSCs) that self-renew, maintain pluripotency, have elongated telomeres, and provide an unlimited source of autologous T cells for immunotherapy. Here, we present a protocol to generate iPSCs using Sendai virus vectors for the transduction of reprogramming factors into TILs. This protocol generates fully reprogrammed, vector-free clones. These TIL-derived iPSCs might be able to generate less-differentiated patient- and tumor-specific T cells for adoptive T cell therapy.
authors.affiliation: Department of Surgery, University of Michigan; Department of Biochemistry II, Kanazawa Medical University.
authors.forename: Hidehito
authors.initials: H
authors.lastname: Saito
authors.affiliation: Center for Immunotherapy, Roswell Park Cancer Institute.
authors.forename: Kumiko
authors.initials: K
authors.lastname: Iwabuchi
authors.affiliation: DNAVEC Corporation; Department of Ophthalmology, Keio University School of Medicine.
authors.forename: Noemi
authors.initials: N
authors.lastname: Fusaki
authors.affiliation: Center for Immunotherapy, Roswell Park Cancer Institute; Department of Surgical Oncology, Roswell Park Cancer Institute; fumito.ito@roswellpark.org.
authors.forename: Fumito
authors.initials: F
authors.lastname: Ito
mesh_terms: D019264:Adoptive Transfer; D006801:Humans; D016219:Immunotherapy, Adoptive; D057026:Induced Pluripotent Stem Cells; D016246:Lymphocytes, Tumor-Infiltrating; D008545:Melanoma / Q000473:pathology*