Enhanced cytolytic activity of tumor infiltrating lymphocytes (TILs) derived from an ICAM-1 transfected tumor in a murine model.
BACKGROUND
Tumors transfected with intercellular adhesion molecule-1 (ICAM-1), a known activator of resting T-cells, show an increased response to adoptive immunotherapy in vivo. This salutary effect may be due to increased sensitivity of the transfected tumor cells to cell-mediated cytotoxicity or an increased activity of the effector cells in the presence of increased amounts of ICAM-1.


METHODS
MCA105 fibrosarcoma cells were transfected with the gene for ICAM-1, and a clone (Cl149) demonstrating significantly increased expression of ICAM-1 by fluorescent-activated cell sorter (FACS) and enzyme-linked immunosorbent assay (ELISA) compared to parental tumor was selected and cultured. Tumor infiltrating lymphocytes (TILs) were cultured in vitro from MCA105 and Cl149 tumors. K562 tumor cells were used as controls.


RESULTS
TILs derived from MCA105 tumors lysed MCA105 (32% at 40:1) and Cl149 (52% at 40:1) target cells but not K562 (3%) demonstrating TIL specificity. TILs derived from Cl149 showed increased lysis of both target cells tested: MCA105 (62% at 40:1, P < 0.05) and Cl149 (98%) compared to lysis of the same target cells by MCA105 TILs as well as being specific (K562, 1%).


CONCLUSIONS
These studies demonstrate that increased expression of ICAM-1 by a tumor cell results in increased lysis by TILs derived from either a tumor with enhanced ICAM-1 expression or a parental tumor, compared to the lysis of parental tumor target cells. In addition, TILs derived from a tumor with enhanced expression of ICAM-1 have significantly increased antitumor efficacy compared to TILs from the parental tumor, suggesting a possible mechanism for previously observed in vivo antitumor effects. These results suggest a new strategy for improving the efficacy of adoptive immunotherapy, by using lymphocytes derived from genetically altered tumors. The study of lymphocytes from genetically modified tumor cells may enable the elucidation of properties of various molecules believed important in cellular cytotoxicity.
Lefor
A T
AT
Department of Surgery, Kern Medical Center, Bakersfield, California 93305, USA. alefor@ucsd.edu
Fabian
D F
DF
D000818:Animals; D003602:Cytotoxicity, Immunologic; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005354:Fibrosarcoma / Q000276:immunology / Q000378:metabolism; D005434:Flow Cytometry; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000502:physiology*; D015979:Killer Cells, Lymphokine-Activated / Q000276:immunology; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D014162:Transfection; D014407:Tumor Cells, Cultured
D018799:Intercellular Adhesion Molecule-1