       Document 0199
 DOCN  M9610199
 TI    Antibody-targeted superantigens are potent inducers of
       tumor-infiltrating T lymphocytes in vivo.
 DT    9601
 AU    Dohlsten M; Hansson J; Ohlsson L; Litton M; Kalland T; Pharmacia
       Oncology Immunology, Lund, Sweden.
 SO    Proc Natl Acad Sci U S A. 1995 Oct 10;92(21):9791-5. Unique Identifier :
       AIDSLINE MED/96003865
 AB    Recruitment of antigen-specific tumor-infiltrating lymphocytes (TILs) is
       a major goal for immunotherapy of malignant tumours. We now describe
       that T-cell-activating superantigens targeted to a tumor by monoclonal
       antibodies induced large numbers of pseudospecific TILs and eradication
       of micrometastases. As a model for tumor micrometastases, syngeneic B16
       melanoma cells transfected with the human colon carcinoma antigen C215
       were injected intravenously into C57BL/6 mice and therapy with an
       anti-C215 Fab fragment-staphylococcal enterotoxin A (C215Fab-SEA) fusion
       protein reacting with the C215 antigen was initiated when visible lung
       metastases were established. More than 90% reduction of the number of
       lung metastases was observed when mice carrying 5-day-old established
       lung metastases were treated with C215Fab-SEA. The antitumor effect of
       C215Fab-SEA was shown to be T-cell-dependent since no therapeutic effect
       was seen in T-cell-deficient nude mice. Depletion of T-cell subsets by
       injection of monoclonal antibody demonstrated that CD8+ cells were the
       most prominent effector cells although some contribution from CD4+ cells
       was also noted. C215Fab-SEA treatment induced massive tumor infiltration
       of CD4+ and CD8+ T cells, while only scattered T cells were observed in
       untreated tumors. SEA treatment alone induced a slight general
       inflammatory response in the lung parenchyme, but no specific
       accumulation of T cells was seen in the tumor. TILs induced by
       C215Fab-SEA were mainly CD8+ but a substantial number of CD4+ cells were
       also present. Immunohistochemical analysis showed strong production of
       the tumoricidal cytokines tumor necrosis factor alpha and interferon
       gamma in the tumor. Thus, the C215Fab-SEA fusion protein targets
       effector T lymphocytes to established tumors in vivo and provokes a
       strong local antitumor immune response.
 DE    Animal  Antibodies, Monoclonal/THERAPEUTIC USE  Antigens,
       Neoplasm/IMMUNOLOGY  Cytokines/METABOLISM  CD4-Positive T-Lymphocytes
       CD8-Positive T-Lymphocytes  Enterotoxins/IMMUNOLOGY/*THERAPEUTIC USE
       Immunoglobulins, Fab/IMMUNOLOGY/*THERAPEUTIC USE  Lung
       Neoplasms/SECONDARY  Lymphocytes, Tumor-Infiltrating/*IMMUNOLOGY
       Melanoma, Experimental/*DRUG THERAPY/IMMUNOLOGY/PATHOLOGY  Mice  Mice,
       Inbred C57BL  Mice, Nude  Staphylococcus aureus/*IMMUNOLOGY
       Superantigens/IMMUNOLOGY/*THERAPEUTIC USE  JOURNAL ARTICLE

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

