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Biological response modifiers (BRM) as antigens. III. T cell lines specific for BRM kill tumor cells in a
1Second Division of Internal Medicine, Kyoto University Faculty of Medicine, Japan.
Abstract:
In order to investigate tumoricidal effector cells in therapy by biological response modifiers (BRM) such as Propionibacterium acnes, bacillus Calmette-Guérin (BCG), Streptococcus pyogenes and a protein-bound polysaccharide (PSK), we established T cell lines specific for each BRM from BALB/c mice immunized with the corresponding BRM. These T cell lines proliferated and produced interleukin-2 (IL-2) and/or IL-4, but only in the presence of the relevant BRM and BALB/c spleen cells as the antigen and antigen-presenting cells respectively. Cross-functional experiments indicated that each BRM acts as a nominal antigen, but not as a non-specific immunostimulator. In addition, the T cell lines killed Ia-positive syngeneic B lymphoma cells, but only in the presence of the relevant BRM. These experiments excluded the possibility of cytotoxic effects by each BRM. The T cell lines and clones also killed Ia-negative bystander target cells, but only in the presence of both a relevant antigen and antigen-presenting cells. The T cell clones specific for S. pyogenes or P. acnes tested were Thy1+, L3T4+ and Lyt2-. These results indicate that some BRM exert tumoricidal activity by inducing T cells that recognize them as an antigen and kill tumor cells in an antigen-specific manner. The T cells killed tumor targets in either a tumor-necrosis-factor(TNF)-dependent or a TNF-independent manner. The mediator of the latter pathway remains to be elucidated.
Insights
Biological response modifiers (BRMs) like Propionibacterium acnes and bacillus Calmette-Guérin induce tumoricidal effector cells. These T cells recognize BRMs as antigens, mediating tumor cell killing in an antigen-specific manner.
Area of Science:
- Immunology
- Cancer Therapy
- Cellular Immunology
Background:
- Biological response modifiers (BRMs) are investigated for cancer therapy.
- The precise mechanisms of BRM-induced tumoricidal activity require elucidation.
- T cell involvement in BRM therapy is a key area of research.
Purpose of the Study:
- To investigate the role of tumoricidal effector cells in BRM therapy.
- To determine if BRMs act as specific antigens or non-specific immunostimulators.
- To characterize the T cell lines generated against various BRMs.
Main Methods:
- Generation of BRM-specific T cell lines from immunized mice.
- Assessing T cell proliferation and cytokine production (IL-2, IL-4) in response to BRMs.
- Evaluating T cell-mediated cytotoxicity against tumor cells (syngeneic B lymphoma cells).
- Phenotypic characterization of T cell clones (Thy1+, L3T4+, Lyt2-).
Main Results:
- BRM-specific T cell lines proliferated and produced cytokines in the presence of relevant BRMs and antigen-presenting cells.
- Each BRM functioned as a nominal antigen, not a non-specific immunostimulator.
- T cell lines demonstrated antigen-specific killing of Ia-positive tumor cells, excluding direct BRM cytotoxicity.
- T cell clones exhibited antigen-specific killing of both syngeneic and bystander tumor cells.
- T cells mediated tumoricidal activity via TNF-dependent or TNF-independent pathways.
Conclusions:
- Certain BRMs induce tumoricidal activity through antigen-specific T cells.
- T cells recognize BRMs as antigens and subsequently kill tumor cells.
- The findings highlight a novel mechanism of BRM-mediated cancer immunotherapy.