Kuby, Immunology, copyright 1992
Tumor cells are poor inducers of an immune response primarily because of their down-presentation of the co-stimulatory B7 molecule and MHC class I molecules both needed for activation of T cells. In addition, tumor cells do not secrete cytokines needed to attract professional antigen presenting cells (APCs). An approach being studied is to introduce certain genes encoding cytokines or co-stimulatory molecules into tumor cells in order to up-regulate expression of these molecules and thus increase the immune response against tumors.
Interferon alpha was the first cytokine gene encoded into tumor cells to be used in clinical trials which showed some efficacy against certain human cancers. Tumor cells engineered to express GM-CSF have markedly enhanced systematic immunity against subsequent challenge with un-treated tumor cells. Currently IL-2, GM-CSF, IL-7 and IL-12 have been shown to induce tumor rejection after immunization with some tumors. Currently underway are phase II trials aimed at studying the effectiveness of vaccines made from tumor cells with or without GM-CSF followed by IL-2. Phase I trials are being studied to determine the effectiveness of using IL-2 gene modified neuroblastoma cells in treating children with relapsed neuroblastoma.
An alternative approach involves the introduction of foreign antigens such as viral antigens into tumor cells in vitro and then re-injecting these altered cells back into the host. This has been shown to induce a strong DTH response which subsequently can lead to the activation of tumor-reactive T cells. The main drawback of introducing a viral antigen into a tumor is that the strong response may eliminate the genetically modified tumor cells too rapidly to allow the development of t cells reactive with the wild-type tumor.
The introduction of B7 genes into tumors has been shown to enhance their immunogenicity leading to an effective immune response against the wild type tumors. In mice models, this B7 co-stimulation leads to expansion of the hierarchy of tumor epitopes that can be recognized. It is hoped that a similar vaccine might prevent metastasis after surgical removal of a primary cancer in humans.