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A human T cell line engineered to secrete chimeric monoclonal antibody
K Y Tsang1, S V Kashmiri, R De Filippi
1Laboratory of Tumor Immunology and Biology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892.
Journal of Immunotherapy with Emphasis on Tumor Immunology : Official Journal of the Society for Biological Therapy
|April 1, 1993
Summary
Researchers engineered human T cells to secrete chimeric antibodies, creating an "antibody factory" at tumor sites. This novel approach combines T cell therapy with monoclonal antibodies (MAbs) for enhanced antitumor effects via antibody-dependent cell-mediated cytotoxicity (ADCC).
Area of Science:
- Immunology
- Oncology
- Biotechnology
Background:
- Monoclonal antibodies (MAbs) and T cells are key in tumor immunotherapy.
- Antibody-dependent cell-mediated cytotoxicity (ADCC) mediated by MAbs shows antitumor effects.
- Combining T cells and MAbs offers a novel therapeutic strategy.
Purpose of the Study:
- To engineer human T cells to secrete chimeric antitumor immunoglobulins (Ig).
- To create a T cell-based system for localized MAb production at tumor sites.
- To evaluate the efficacy of secreted chimeric Ig in mediating ADCC.
Main Methods:
- Cloned D612 MAb Ig genes and generated a chimeric D612 IgG1 (murine variable, human constant regions).
- Transfected the chimeric D612 gene into the human T-cell line MOLT-4.
- Assayed antigen-binding and ADCC activity of secreted Ig.
Main Results:
- Chimeric D612 was successfully expressed and secreted by MOLT-4 T cells (0.25 µg/mL/10^6 cells in 72 hours).
- Secreted Ig retained antigen-binding capacity and mediated ADCC against human tumor cells.
- This is the first demonstration of chimeric IgG production by human T cells.
Conclusions:
- Human T cells can be engineered to function as factories for secreting chimeric antitumor MAbs.
- This approach enables localized MAb-mediated ADCC at the tumor site, enhancing immunotherapy.
- This represents a potential new therapeutic strategy for cancer treatment.