Growth of tumor-infiltrating lymphocytes from human solid cancers: summary of a 5-year experience.
Between 1989 and 1993, 255 tumor biopsies representing 4 tumor histologies (melanoma, breast cancer, colon cancer and renal cell cancer) were received by the Surgery Branch of the National Cancer Institute. Tumor-infiltrating lymphocytes (TIL) were grown from single-cell suspensions of tumor biopsies over the course of 30-45 days. The TIL were grown in medium containing IL-2. To obtain numbers suitable for therapy (>10(11)), TIL were expanded using a large-scale system of cell culture and harvesting. While the largest number of biopsies was obtained from melanoma patients, TIL were successfully grown from 160 of 255 tumor biopsies representing all 4 histologies. Under the culture conditions employed, several characteristics of TIL expansion were observed. The cell surface phenotype of TIL which grew out from the tumor biopsies was generally a mix of CD3+/CD4+ or CD3+/CD8+ lymphocytes. Only TIL from melanoma biopsies were found to be consistently cytolytic and, in many cases, lysed autologous tumor cells preferentially. Interestingly, TIL derived from extra-nodal sites of metastatic melanoma biopsies (subcutaneous, lung, bowel; 36 of 67, 54%) were more likely to have these cytolytic characteristics than TIL derived from tumor-involved lymph node biopsies (7 of 39, 18%). The present study summarizes 5 years of laboratory effort and validates the technologies developed for the large-scale growth and harvesting of TIL. In addition, it summarizes the laboratory effort supporting previously published clinical reports on TIL from our group.
Yannelli
J R
JR
National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
Hyatt
C
C
McConnell
S
S
Hines
K
K
Jacknin
L
L
Parker
L
L
Sanders
M
M
Rosenberg
S A
SA
D001943:Breast Neoplasms / Q000276:immunology / Q000473:pathology; D002292:Carcinoma, Renal Cell / Q000276:immunology / Q000473:pathology; D002478:Cells, Cultured; D003110:Colonic Neoplasms / Q000276:immunology / Q000473:pathology; D003602:Cytotoxicity, Immunologic; D006801:Humans; D016219:Immunotherapy, Adoptive; D007680:Kidney Neoplasms / Q000276:immunology / Q000473:pathology; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D008545:Melanoma / Q000276:immunology / Q000473:pathology; D009369:Neoplasms / Q000628:therapy*; D013535:Suspensions
D013535:Suspensions