       Document 0280
 DOCN  M9640280
 TI    Culture of tumour-infiltrating lymphocytes from melanoma and colon
       carcinoma: removal of tumour cells does not affect tumour-specificity.
 DT    9604
 AU    Mulder WM; Stukart MJ; Roos M; van Lier RA; Wagstaff J; Scheper RJ;
       Bloemena E; Department of Pathology, Free University Hospital,
       Amsterdam, The; Netherlands.
 SO    Cancer Immunol Immunother. 1995 Nov;41(5):293-301. Unique Identifier :
       AIDSLINE MED/96132673
 AB    The therapeutic potential of adoptive therapy using tumour-infiltrating
       lymphocytes (TIL) has been demonstrated in a number of clinical trials.
       However, freshly isolated tumour-infiltrating lymphocytes (TIL) are
       often impaired in their proliferative and cytotoxic responses, which
       limits their use in immunotherapy. Several hypotheses with regard to the
       poor effector function of TIL have been postulated, including the
       production of immunosuppressive factors by tumour cells. In a previous
       paper we reported the efficient expansion of immunoreactive TIL from a
       variety of solid tumours by stimulation with a combination of monoclonal
       antibodies (mAbs) against CD3 and CD28. In the present study we analysed
       whether this protocol would be improved by the removal of tumour cells
       at the start of the culture. We tested a highly immunogenic tumour,
       melanoma, and a poorly immunogenic tumour, colon carcinoma. Removal of
       tumour cells highly improved anti-CD3/CD28 stimulated expansion of TIL
       from colon carcinoma, resulting in a significantly higher percentage of
       potentially tumour-specific CD8-positive T-cells and a reduced CD4/CD8
       ratio compared to expansion in the presence of tumour cells. In
       contrast, expansion and CD4/CD8 ratio of melanoma-derived TIL was not
       significantly influenced by the removal of autologous tumour cells.
       CD3/CD28-stimulated melanoma TIL cultured in the absence of tumour cells
       showed specific lysis of autologous tumour cells comparable to melanoma
       TIL cultured in high-dose IL2. However, no cytotoxicity could be
       detected in colon TIL irrespective of the culture conditions used. On
       the other hand, 3/8 colon carcinoma TIL cultures and 9/12
       melanoma-derived TIL cultures showed IFN gamma secretion upon
       stimulation with autologous tumour cells. We conclude that stimulation
       of TIL with a combination of mAbs to CD3 and CD28 in the absence of
       tumour cells induces efficient expansion of potentially tumour-specific
       cells from a highly and a poorly immunogenic tumour. Removal of tumour
       cells does not have a negative influence on the generation of
       tumour-specific T cells, while cell yield improves. Therefore, for
       large-scale cultures this protocol can efficiently induce the outgrowth
       of tumour-specific TIL, at the same time providing a useful source of
       autologous tumour cells that can be stored and used to direct or test
       antitumour specificity.
 DE    Antibodies, Monoclonal/IMMUNOLOGY  Antigens, CD28/IMMUNOLOGY  Antigens,
       CD3/IMMUNOLOGY  Cells, Cultured  Colonic Neoplasms/*IMMUNOLOGY
       *Cytotoxicity, Immunologic  CD4-CD8 Ratio  Human  Immunophenotyping
       Interferon Type II/SECRETION  Interleukin-2/PHARMACOLOGY  Lymphocytes,
       Tumor-Infiltrating/*IMMUNOLOGY  Melanoma/*IMMUNOLOGY  Sensitivity and
       Specificity  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).

