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Experimental and clinical studies of cytokine gene-modified tumor cells
1Laboratory of Tumor Biology, Massachusetts General Hospital Cancer Center, Charlestown 02129.
Abstract:
Cytokines are key modulators of host immune and inflammatory responses. The expression of cytokine genes by tumor cells as a result of gene transfer has emerged as a novel strategy to augment in vivo host reactivity to various cancers. This review summarizes the knowledge obtained from experimental systems using this strategy and provides information on the current clinical trials employing this approach. In murine model systems, immunization with tumors expressing certain cytokines [e.g., tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), interleukin-7 (IL-7), and granulocyte-macrophage colony stimulating (GM-CSF)] has demonstrated their ability to promote the generation of tumor-specific cytotoxic T lymphocytes by various mechanisms; in some cases, significant regressions of established microscopic tumor deposits result. Non T cell mechanisms of tumor killing, such as granulocytic inflammatory responses, may also be elicited by the localized elaboration of certain cytokines [e.g., IL-4, granulocyte colony-stimulating factor (G-CSF)]. The potency of antitumor immune potentiation by cytokines, however, remains to be established by further animal studies and emerging clinical trials. The genetic modification of tumors for the expression of immunostimulatory gene products holds promise as a new approach for active immunotherapy of cancer and for the isolation of effector cell populations for use in adoptive immunotherapy protocols.
Insights
Gene transfer into tumor cells to express cytokines enhances anti-tumor immunity. This immunotherapy approach shows promise in experimental models and early clinical trials for cancer treatment.
Area of Science:
- Immunology
- Oncology
- Gene Therapy
Background:
- Cytokines are crucial regulators of immune and inflammatory responses.
- Tumor cells genetically modified to express cytokines offer a novel strategy to enhance anti-cancer immunity.
- This approach aims to boost the host's immune system against various cancers.
Purpose of the Study:
- To review experimental findings on cytokine gene transfer in tumors.
- To provide an overview of current clinical trials using this immunotherapy.
- To assess the potential of cytokine-expressing tumors in cancer treatment.
Main Methods:
- Review of experimental systems using gene transfer to express cytokines in tumor cells.
- Analysis of data from murine models demonstrating anti-tumor immune responses.
- Compilation of information from ongoing clinical trials.
Main Results:
- Tumors engineered to express cytokines like TNF-alpha, IL-6, IL-7, and GM-CSF can induce tumor-specific cytotoxic T lymphocytes.
- These modifications have led to significant regressions of microscopic tumors in some murine models.
- Localized cytokine release can also trigger non-T cell mediated tumor killing, such as granulocytic inflammatory responses.
Conclusions:
- Cytokine gene transfer into tumors is a promising strategy for active cancer immunotherapy.
- Further animal studies and clinical trials are needed to establish the full potency of this approach.
- This method may also aid in isolating effector cells for adoptive immunotherapy.