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Induction of immune responsiveness in a genetically low-responsive tumor-host combination by chemical modification of
Abstract:
Trinitrophenylated Moloney virus-induced YAC cells induced a higher cytotoxic antibody response and better protection against small tumor cell doses in syngeneic, low-responsive strain A mice than nonmodified YAC cells that had been inactivated by irradiation or mitomycin C treatment. The results indicated that genetically determined low responsiveness to a virally induced antigen can be overcome, at least to some extent, by coupling the immunizing cells to a strong immunogenic hapten.
Insights
Coupling Moloney virus-induced YAC cells to a strong immunogenic hapten, trinitrophenyl, enhanced cytotoxic antibody response and tumor protection in low-responsive mice. This approach can overcome genetic low responsiveness to viral antigens.
Area of Science:
- Immunology
- Virology
- Oncology
Background:
- Genetic factors influence immune responses to viral antigens.
- Low responsiveness can hinder effective anti-tumor immunity.
- Moloney virus-induced YAC cells are a model for studying viral antigen responses.
Purpose of the Study:
- To investigate if hapten modification of viral antigen-presenting cells can overcome genetic low immune responsiveness.
- To evaluate the efficacy of trinitrophenylated YAC cells in inducing protective anti-tumor immunity.
Main Methods:
- YAC cells induced by Moloney murine leukemia virus were modified with trinitrophenyl (TNP).
- These modified cells were used for immunization in syngeneic, low-responsive strain A mice.
- Immune response was assessed by cytotoxic antibody levels and protection against tumor cell challenge.
Main Results:
- Trinitrophenylated YAC cells elicited a significantly higher cytotoxic antibody response compared to nonmodified YAC cells.
- Immunization with modified YAC cells provided better protection against small tumor cell doses.
- Nonmodified YAC cells, inactivated by irradiation or mitomycin C, were less effective.
Conclusions:
- Hapten modification of viral antigen-presenting cells can overcome genetically determined low responsiveness.
- Trinitrophenyl modification represents a potential strategy to enhance anti-viral and anti-tumor immunity in low responders.