Perforin and IFN-γ are involved in the antitumor effects of antibody- targeted superantigens
Rosendahl, Alexander ; Kristensson, Karin ; Hansson, Johan ; Riesbeck, Kristian LU
; Kalland, Terje
and Dohlsten, Mikael
(1998)
In Journal of Immunology
160(11).
p.5309-5313
- Abstract
The bacterial superantigen staphylococcal enterotoxin A (SEA) is a potent inducer of cytokine production and cytotoxic T cell responses. To target a T cell attack against tumor cells we have genetically engineered a fusion protein of SEA and the Fab part of the tumor-reactive mAb C215. Injection of this Fab-SEA fusion protein to mice carrying lung metastases of the poorly immunogenic B16 melanoma transfected with the C215 Ag resulted in infiltration of cytokine-producing T cells, perforin-containing CTL, and a marked tumor elimination. Fab-SEA therapy induced substantial levels of IFN- γ and TNF-α in serum. In the present study we have characterized the molecular mechanisms of the antitumor effect induced by Fab-SEA treatment in vivo.... (More)
The bacterial superantigen staphylococcal enterotoxin A (SEA) is a potent inducer of cytokine production and cytotoxic T cell responses. To target a T cell attack against tumor cells we have genetically engineered a fusion protein of SEA and the Fab part of the tumor-reactive mAb C215. Injection of this Fab-SEA fusion protein to mice carrying lung metastases of the poorly immunogenic B16 melanoma transfected with the C215 Ag resulted in infiltration of cytokine-producing T cells, perforin-containing CTL, and a marked tumor elimination. Fab-SEA therapy induced substantial levels of IFN- γ and TNF-α in serum. In the present study we have characterized the molecular mechanisms of the antitumor effect induced by Fab-SEA treatment in vivo. Neutralization of cytokines by specific Abs demonstrated a major role for IFN-γ in the suppression of tumor growth. In addition, a minor contribution of TNF-α was recorded. Injections of Fab-SEA into normal mice induced strong CTL activity but failed to promote cytotoxic function in perforin knockout mice. Also, a markedly reduced therapy was noted in perforin knockout mice, implicating a role for CTL in Fab-SEA-mediated tumor eradication. The data suggest that Fab-SEA-targeted T cells may suppress tumor growth by both perforin-dependent cytotoxicity and local release of cytokines such as IFN-γ. The latter mechanism may have an important role in cytostatic effects against Ag-negative bystander tumor cells.
(Less)
- author
- Rosendahl, Alexander
; Kristensson, Karin
; Hansson, Johan
; Riesbeck, Kristian
LU
; Kalland, Terje
and Dohlsten, Mikael
- publishing date
- 1998-06-01
- type
- Contribution to journal
- publication status
- published
- in
- Journal of Immunology
- volume
- 160
- issue
- 11
- pages
- 5309 - 5313
- publisher
- American Association of Immunologists
- external identifiers
-
- scopus:0032104007
- pmid:9605129
- ISSN
- 0022-1767
- language
- English
- LU publication?
- no
- id
- 4d84ec84-45ac-4662-9a70-765160e8df8d
- alternative location
- https://www.jimmunol.org/content/jimmunol/160/11/5309.full.pdf
- date added to LUP
- 2019-06-07 15:23:34
- date last changed
- 2024-03-19 12:06:08
@article{4d84ec84-45ac-4662-9a70-765160e8df8d,
abstract = {{<p>The bacterial superantigen staphylococcal enterotoxin A (SEA) is a potent inducer of cytokine production and cytotoxic T cell responses. To target a T cell attack against tumor cells we have genetically engineered a fusion protein of SEA and the Fab part of the tumor-reactive mAb C215. Injection of this Fab-SEA fusion protein to mice carrying lung metastases of the poorly immunogenic B16 melanoma transfected with the C215 Ag resulted in infiltration of cytokine-producing T cells, perforin-containing CTL, and a marked tumor elimination. Fab-SEA therapy induced substantial levels of IFN- γ and TNF-α in serum. In the present study we have characterized the molecular mechanisms of the antitumor effect induced by Fab-SEA treatment in vivo. Neutralization of cytokines by specific Abs demonstrated a major role for IFN-γ in the suppression of tumor growth. In addition, a minor contribution of TNF-α was recorded. Injections of Fab-SEA into normal mice induced strong CTL activity but failed to promote cytotoxic function in perforin knockout mice. Also, a markedly reduced therapy was noted in perforin knockout mice, implicating a role for CTL in Fab-SEA-mediated tumor eradication. The data suggest that Fab-SEA-targeted T cells may suppress tumor growth by both perforin-dependent cytotoxicity and local release of cytokines such as IFN-γ. The latter mechanism may have an important role in cytostatic effects against Ag-negative bystander tumor cells.</p>}},
author = {{Rosendahl, Alexander and Kristensson, Karin and Hansson, Johan and Riesbeck, Kristian and Kalland, Terje and Dohlsten, Mikael}},
issn = {{0022-1767}},
language = {{eng}},
month = {{06}},
number = {{11}},
pages = {{5309--5313}},
publisher = {{American Association of Immunologists}},
series = {{Journal of Immunology}},
title = {{Perforin and IFN-γ are involved in the antitumor effects of antibody- targeted superantigens}},
url = {{https://www.jimmunol.org/content/jimmunol/160/11/5309.full.pdf}},
volume = {{160}},
year = {{1998}},
}