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Subsets of oncofetal antigen-induced T-cells: ability to mediate antitumor immune response
Abstract:
The present study was performed to identify the subsets of oncofetal antigen-induced T-cells that mediate antitumor immune response in mice. In this study, performed on a weakly immunogenic, metastatic tumor, fetal antigen-sensitized spleen cells significantly inhibited the growth and metastases of tumors in Winn neutralization assay. Mixing of spleen cells from tumor-bearing inbred C57BL/6J mice with fetal antigen-sensitized spleen cells completely abolished the tumor inhibitory effect of fetal antigen-sensitized spleen cells. Further characterization of fetal antigen-sensitized spleen cells showed that they were Thy-1+. These findings reveal that tumor-associated fetal antigens on fetal cells can produce a tumor inhibitory T-cell immune response against the growth and metastases of a weakly immunogenic, metastatic tumor. The subset of oncofetal antigen-induced T-cells that mediates antitumor immune response was identified as Lyt-1+ and Lyt-2-. Adoptive transfer of fetal antigen-sensitized spleen cells to mice with preestablished metastases significantly inhibited the lung metastases in these mice, thus making this approach more relevant to a clinical situation in cancer patients.
Insights
Tumor-associated fetal antigens induce T-cells that inhibit cancer growth and metastasis in mice. These specific T-cells (Lyt-1+, Lyt-2-) offer potential for cancer immunotherapy.
Area of Science:
- Immunology
- Oncology
Background:
- Tumor-associated antigens (TAAs) are crucial targets for cancer immunotherapy.
- Oncofetal antigens are TAAs expressed during fetal development and re-expressed in certain cancers.
- Understanding T-cell subsets mediating antitumor responses is vital for therapeutic development.
Purpose of the Study:
- To identify T-cell subsets induced by oncofetal antigens that mediate antitumor immunity.
- To evaluate the efficacy of fetal antigen-sensitized T-cells against weakly immunogenic, metastatic tumors.
- To assess the therapeutic potential of adoptive T-cell transfer in preclinical cancer models.
Main Methods:
- Winn neutralization assay using spleen cells from fetal antigen-sensitized mice.
- Characterization of T-cell subsets using surface markers (Thy-1, Lyt-1, Lyt-2).
- Adoptive transfer of sensitized spleen cells into tumor-bearing mice with pre-established lung metastases.
Main Results:
- Fetal antigen-sensitized spleen cells significantly inhibited tumor growth and metastasis.
- Tumor-bearing mouse spleen cells abrogated the inhibitory effect of sensitized cells, indicating T-cell involvement.
- The antitumor T-cells were identified as Lyt-1+ and Lyt-2-.
- Adoptive transfer of sensitized cells reduced lung metastases in mice with established disease.
Conclusions:
- Oncofetal antigen-induced T-cells, specifically Lyt-1+ and Lyt-2-, mediate significant antitumor immune responses.
- This T-cell subset effectively inhibits the growth and metastasis of weakly immunogenic tumors.
- Adoptive transfer of these T-cells demonstrates therapeutic potential for established metastases, relevant to clinical cancer treatment.