Priming for T-cell-mediated rejection of established tumors by cutaneous DNA immunization
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Published on: February 24, 2023
1The Immunology Program, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
Abstract:
DNA immunization has been shown to elicit both antibody and CTL responses against antigens expressed by infectious organisms. Because CTL responses have been implicated in rejection of cancer, we investigated whether DNA immunization by particle bombardment using a gene gun could induce CTL responses that were capable of rejecting tumors in mice. DNA immunization by particle bombardment using genes encoding beta-galactosidase and ovalbumin primed mice to generate CTLs in two genetic backgrounds (DBA/2 and C57BL/6 strains, respectively). DNA immunization was more potent in inducing CTLs than immunization with an optimized regimen of ovalbumin peptide plus immune adjuvant. Immunity induced by DNA immunization protected mice against s.c. challenge with tumors expressing the beta-galactosidase antigen. Tumors were rejected even when DNA immunization was started 3 or 7 days after tumor challenge as tumors were becoming established. Tumor rejection required CD8(+) T cells, confirming a role for CTLs in vivo. These studies show that DNA immunization by particle bombardment can efficiently induce CTL responses that are capable of rejecting even established tumors.
Insights
DNA immunization using a gene gun effectively generates cytotoxic T lymphocyte (CTL) responses. This method successfully rejected established tumors in mice, highlighting its potential for cancer immunotherapy.
Area of Science:
- Immunology
- Cancer Research
- Gene Therapy
Background:
- DNA immunization elicits antibody and cytotoxic T lymphocyte (CTL) responses against infectious agents.
- CTL responses play a role in cancer rejection.
- Particle bombardment (gene gun) is a method for DNA delivery.
Purpose of the Study:
- To investigate if DNA immunization via particle bombardment can induce CTL responses capable of rejecting tumors in mice.
- To assess the potency of DNA immunization for CTL induction compared to peptide immunization.
- To determine if DNA immunization can reject established tumors.
Main Methods:
- Mice were immunized using DNA encoding beta-galactosidase or ovalbumin via particle bombardment.
- CTL responses were generated in DBA/2 and C57BL/6 mouse strains.
- Mice were challenged with tumors expressing beta-galactosidase.
- Tumor rejection was assessed, and the role of CD8(+) T cells was confirmed.
Main Results:
- DNA immunization via particle bombardment primed mice to generate CTLs.
- This method was more potent in inducing CTLs than optimized peptide immunization.
- DNA immunization protected mice against established tumors expressing beta-galactosidase.
- Tumor rejection occurred even when immunization started after tumor establishment.
- Tumor rejection was dependent on CD8(+) T cells.
Conclusions:
- DNA immunization by particle bombardment efficiently induces potent CTL responses.
- This approach can lead to the rejection of established tumors in a mouse model.
- DNA immunization represents a promising strategy for cancer immunotherapy.
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