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 histolo gies (melanoma, breast cancer, colon cancer and renal cell cancer) wer e received by the Surgery Branch of the National Cancer Institute. Tum or-infiltrating lymphocytes (TIL) were grown from single-cell suspensi ons of tumor biopsies over the course of 30-45 days. The TIL were grow n 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 fro m 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. Onl y TIL from melanoma biopsies were found to be consistently cytolytic a nd, in many cases, lysed autologous tumor cells preferentially. Intere stingly, TIL derived from extra-nodal sites of metastatic melanoma bio psies (subcutaneous, lung, bowel; 36 of 67, 54%) were more likely to h ave these cytolytic characteristics than TIL derived from tumor-involv ed lymph node biopsies (7 of 39, 18%). The present study summarizes 5 years of laboratory effort and validates the technologies developed fo r the large-scale growth and harvesting of TIL. In addition, it summar izes the laboratory effort supporting previously published clinical re ports on TIL from our group. (C) 1996 Wiley-Liss, Inc.