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Clinical trials targeting advanced cancers by active immunization of T-cell defined tumor antigens
1Department of Clinical Pathology, Sapporo Medical University School of Medicine S-1, W-16, Chuo-ku Sapporo 060-8543. hikeda@sapmed.ac.jp
Abstract:
Identification of CD8(+) and CD4(+) T-cell defined tumor antigens has opened the way for possible cancer immunotherapy. Peptide-based active immunization has begun mainly targeting melanoma. Surprisingly, some objective responses were obtained in the initial trials, leading to the accumulation of an explosive number of such antigens. Serological screening of cDNA expression libraries accelerated the identification of immunodominant antigens, resulting in the emergence of the concept of a "cancer-testis antigen." On the other hand, an advance in basic immunology has been promptly adopted: dendritic cells, as potent professional antigen presenting cells have been preferentially used in combination with the antigen in clinical trials both in vivo and in vitro. Tetramer analysis provided a powerful tool to directly monitor antigen-specific T cells in vivo in these trials. Moreover, adoptive transfer of antigen-specific T cells has added a new perspective to recent cancer immunotherapy.
Insights
Cancer immunotherapy is advancing with the identification of tumor antigens recognized by T-cells. Researchers are exploring peptide-based vaccines and dendritic cell therapies, alongside T-cell adoptive transfer, for improved cancer treatment outcomes.
Area of Science:
- Immunology
- Oncology
- Cancer Research
Background:
- Identification of T-cell defined tumor antigens enables cancer immunotherapy development.
- Early peptide-based active immunization trials, primarily for melanoma, showed promising objective responses.
- The discovery of immunodominant antigens, including cancer-testis antigens, has rapidly expanded the field.
Purpose of the Study:
- To review the progress and emerging strategies in cancer immunotherapy.
- To highlight the role of tumor antigens and T-cell based approaches.
- To discuss advancements in antigen discovery and T-cell manipulation for therapeutic benefit.
Main Methods:
- Serological screening of cDNA expression libraries for antigen identification.
- Utilizing dendritic cells as antigen-presenting cells in clinical trials.
- Employing tetramer analysis for in vivo monitoring of antigen-specific T cells.
Main Results:
- Objective responses observed in early peptide-based immunotherapy trials.
- Accelerated identification of tumor antigens, including cancer-testis antigens.
- Successful application of dendritic cell-based therapies and adoptive T-cell transfer.
Conclusions:
- Cancer immunotherapy has significantly advanced through the identification of tumor antigens and T-cell based strategies.
- Dendritic cell therapy and adoptive T-cell transfer represent promising frontiers in cancer treatment.
- Continued research into tumor antigens and T-cell manipulation holds potential for more effective cancer immunotherapies.