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Costimulation by CD48 and B7-1 induces immunity against poorly immunogenic tumors
Y Li1, K E Hellstrom, S A Newby
1Bristol-Myers Squibb Pharmaceutical Research Institute, Seattle, Washington 98121, USA.
Abstract:
Genetic modification of many types of mouse tumors to express the B7-1 or B7-2 molecules, natural ligands for the T cell-costimulatory molecule CD28, increases their immunogenicity. However, even after transfection with the B7-1 and/or B7-2 genes, poorly immunogenic tumors fail to elicit and efficient immune response. We report here that two such tumors, the Ag104A sarcoma and the K1735-M2 melanoma, become immunogenic after transfection of the genes encoding murine B7-1 together with CD48, which is the natural ligand for CD2. Tumor-specific CD8+ cytotoxic T lymphocytes were readily generated and were effective for adoptive immunotherapy of metastasis induced by wild-type Ag104A sarcoma cells. A similar approach may be useful for developing therapy for other poorly immunogenic tumors, including those in humans.
Insights
Enhancing tumor immunogenicity for cancer therapy: Combining B7-1 and CD48 gene transfection in mouse models successfully generated anti-tumor immune responses, offering a potential strategy for treating poorly immunogenic tumors.
Area of Science:
- Immunology
- Cancer Biology
- Molecular Genetics
Background:
- Genetic modification of mouse tumors with B7-1 or B7-2 molecules enhances immunogenicity.
- Poorly immunogenic tumors often fail to elicit effective immune responses even after B7 gene transfection.
Purpose of the Study:
- To investigate if co-expression of B7-1 and CD48 can render poorly immunogenic mouse tumors (Ag104A sarcoma, K1735-M2 melanoma) immunogenic.
- To evaluate the potential of this combined gene therapy approach for cancer immunotherapy.
Main Methods:
- Transfection of Ag104A sarcoma and K1735-M2 melanoma cells with genes encoding murine B7-1 and CD48.
- Generation of tumor-specific CD8+ cytotoxic T lymphocytes (CTLs).
- Assessment of CTL efficacy in adoptive immunotherapy against wild-type Ag104A sarcoma-induced metastasis.
Main Results:
- Co-transfection with B7-1 and CD48 genes successfully induced immunogenicity in previously poorly immunogenic tumors.
- Tumor-specific CD8+ CTLs were readily generated.
- Adoptive immunotherapy using these CTLs was effective against metastasis.
Conclusions:
- Combined B7-1 and CD48 gene transfer is a viable strategy to enhance the immunogenicity of poorly immunogenic tumors.
- This approach holds promise for developing novel immunotherapies for various cancers, potentially including human tumors.