Related Experiment Videos
Survivin--a universal tumor antigen
1Tumor Immunology Group, Danish Cancer Society, Copenhagen. mha@cancer.dk
Abstract:
Tumor-associated antigens recognized by cellular effectors of the immune system are potential targets for antigen-specific cancer immunotherapy. These antigens are classified as tissue (melanocyte)-specific proteins, cancer-testis antigens (proteins expressed in normal testis and various cancers), tumor-specific peptides derived from mutations in tumor cells, and others. Clinical studies with peptides and proteins derived from these antigens have been initiated to study the efficacy of inducing specific cytotoxic T lymphocytes (CTL) responses in vivo. However, most of the peptide epitopes used in these vaccination trials are melanocyte-specific, and these peptides cannot be applied for tumors of non-melanocyte origin. Furthermore, the expression of most tumor antigens is heterogeneous among tumors from different patients and can even vary among metastases obtained from one patient. Immune selection of antigen loss variants may prove to be an additional obstacle for the clinical applicability of most of the known CTL epitopes. Recently, a new tumor antigen, survivin, has been identified on the basis of spontaneous CTL responses in different cancer patients. Survivin is expressed in most human neoplasms, but not in normal, differentiated tissues. Importantly, downregulation or loss of survivin would severely inflict the growth potential of the tumor cell. Since survivin is expressed by a variety of different tumors MHC-restricted survivin epitopes may serve as important and widely applicable targets for anti-cancer immunotherapeutic strategies.
Insights
Survivin, a novel tumor antigen, shows promise for cancer immunotherapy. Its expression across many cancers, unlike melanocyte-specific antigens, offers broad therapeutic potential for cytotoxic T lymphocyte (CTL) responses.
Area of Science:
- Immunology
- Oncology
- Biochemistry
Background:
- Tumor-associated antigens are targets for cancer immunotherapy, including tissue-specific proteins, cancer-testis antigens, and mutation-derived peptides.
- Current immunotherapies often use melanocyte-specific antigens, limiting their application to non-melanoma cancers.
- Tumor antigen heterogeneity and immune selection pose challenges for effective cancer immunotherapy.
Purpose of the Study:
- To identify and evaluate novel tumor antigens for broad cancer immunotherapy applications.
- To investigate survivin as a potential universal tumor antigen for inducing cytotoxic T lymphocyte (CTL) responses.
- To overcome limitations of current antigen-specific cancer immunotherapies.
Main Methods:
- Identification of tumor antigens based on spontaneous CTL responses in cancer patients.
- Analysis of survivin expression patterns in various human neoplasms and normal tissues.
- Evaluation of MHC-restricted survivin epitopes as potential targets for anti-cancer strategies.
Main Results:
- Survivin identified as a novel tumor antigen with spontaneous CTL responses in cancer patients.
- Survivin is expressed in most human neoplasms but not in normal differentiated tissues.
- Downregulation of survivin significantly impairs tumor cell growth potential.
Conclusions:
- Survivin represents a widely applicable target for anti-cancer immunotherapeutic strategies due to its broad expression in tumors.
- MHC-restricted survivin epitopes can be utilized to induce specific CTL responses against various cancers.
- Survivin-based immunotherapy offers a promising approach to overcome limitations of current cancer treatments.