       Document 0894
 DOCN  M9590894
 TI    The therapeutic efficacy of murine anti-tumor T cells: freshly isolated
       T cells are more therapeutic than T cells expanded in vitro.
 DT    9509
 AU    Evans R; Kamdar SJ; Duffy TM; Krupke DM; Fuller JA; Dudley ME; Jackson
       Laboratory, Bar Harbor, Maine 04609, USA.
 SO    Anticancer Res. 1995 Mar-Apr;15(2):441-7. Unique Identifier : AIDSLINE
       MED/95283273
 AB    Adoptive immunotherapy (AIT) involving transfer of tumor-sensitized T
       lymphocytes in combination with cyclophosphamide (CY)-injection results
       in the eradication of the C57BL/6J (B6) rhabdomyosarcoma, 76-9 and is
       associated with the accumulation of a large number of tumor-infiltrating
       lymphocytes (TIL). Using immune spleen cells (ISC) from B6 and congenic
       B6. PL. Thy-1a mice, it was shown that most (> or = 97%) of the TIL were
       donor-derived. This in situ increase in donor-derived T cells was
       confirmed by using positively-selected Thy- 1.1+ and Thy- 1.2+ TIL for
       AIT after isolating them from regressing tumors and expanding them in
       rIL-2. The extent of CD8+ TIL expansion in vivo correlated with the
       numbers of TIL adoptively transferred and this in turn determined the
       degree of anti-tumor effects. It was evident, however, that these in
       vitro-expanded TIL expressing mRNA for TNF alpha and IFN gamma were
       qualitatively different and therapeutically less efficacious than the T
       cells associated with ISC or with freshly-isolated TIL. Unlike freshly
       isolated TIL that expressed specific cytotoxicity towards the 76-9
       targets in vitro, IL-2 expanded TIL killed 76-9 cells and unrelated
       tumor targets to the same extent. A cytotoxic CD8+ T cell line derived
       from ISC and selected for activity against the 76-9 tumor cells showed
       no therapeutic efficacy. The data suggest that, in this tumor model,
       expansion of CD8+ T cells in vitro selects against anti-tumor efficacy.
 DE    Animal  Antigens, Thy-1/ANALYSIS  Cell Separation  Cells, Cultured
       Combined Modality Therapy  Comparative Study
       Cyclophosphamide/THERAPEUTIC USE  Cytotoxicity, Immunologic
       CD8-Positive T-Lymphocytes/IMMUNOLOGY/TRANSPLANTATION  *Immunotherapy,
       Adoptive  Lymphocytes, Tumor-Infiltrating/IMMUNOLOGY/*TRANSPLANTATION
       Mice  Mice, Inbred C57BL  Remission Induction  Rhabdomyosarcoma/DRUG
       THERAPY/IMMUNOLOGY/PATHOLOGY/*THERAPY  Soft Tissue Neoplasms/DRUG
       THERAPY/IMMUNOLOGY/PATHOLOGY/*THERAPY  Support, Non-U.S. Gov't  Support,
       U.S. Gov't, P.H.S.  T-Lymphocyte Subsets/IMMUNOLOGY/*TRANSPLANTATION
       JOURNAL ARTICLE

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

