title: Growth and autologous tumor lysis by tumor-infiltrating lymphocytes from metastatic melanoma expanded in interleukin-2 or interleukin-2 plus interleukin-4.
abstract: Optimal conditions for expanding tumor-infiltrating lymphocytes (TILs) specifically cytotoxic for autologous melanoma for clinical use have not yet been identified. In several small studies, interleukin (IL)-4 was reported to promote the growth of such TILs in IL-2. Given the potential implications for TIL therapy, we attempted to confirm these findings in a larger study. Baseline data were first obtained on the proliferation, immunophenotype, and cytotoxic reactivity to autologous melanoma of TILs cultured in IL-2 alone. Similar studies were performed with TIL cultured concurrently in either IL-2 alone or in a combination of IL-2 and IL-4. TILs were obtained by excisional biopsy of tumors from 52 patients with metastatic malignant melanoma; TILs from 38 patients were expanded in IL-2 (1,000 U/ml). TILs from 19 biopsies were maximally expanded 6- to 24,000-fold (median, 300-fold) over 4-10 weeks. Expansion did not correlate with the weight of, or number of lymphocytes in, the biopsy specimen, or the site of the biopsy (lymph node vs. subcutaneous metastases). During weeks 5-8, TILs from 19 of 25 biopsy specimens lysed autologous melanoma with little or no lysis of allogeneic melanoma. Lysis of autologous tumor was blocked by antibody to class I antigens. Twenty-four TIL specimens were cultured concurrently in IL-2 alone and in IL-2 plus IL-4 and tested for growth and for lysis of autologous and allogeneic melanomas.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Division of Oncology, University of Washington, Seattle 98195.
authors.forename: C G
authors.initials: CG
authors.lastname: Lindgren
authors.forename: J A
authors.initials: JA
authors.lastname: Thompson
authors.forename: C M
authors.initials: CM
authors.lastname: Higuchi
authors.forename: A
authors.initials: A
authors.lastname: Fefer
mesh_terms: D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology*; D015847:Interleukin-4 / Q000494:pharmacology*; D016246:Lymphocytes, Tumor-Infiltrating / Q000187:drug effects / Q000276:immunology*; D008545:Melanoma / Q000276:immunology* / Q000473:pathology / Q000556:secondary; D010641:Phenotype
chemical_list: D007376:Interleukin-2; D015847:Interleukin-4