The current protocols of T cell transduction involve in vitro activation to achieve T cell proliferation that is required for effective retroviral infection. Adoptive transfer of such minimally stimulated cells will reveal whether in vivo transfer of TCR transduced resting T cells provides more effective protection from disease and better memory development than transfer of fully activated T cells.
TCR gene transfer can also be used to produce antigen-specific CD4+ helper T cells. The in vivo interaction of conventional CD4+ T cells is restricted to MHC class II-positive professional antigen-presenting cells. Recognition of DC presented antigen triggers the production of cytokines by conventional CD4+ T cells. IL-2 has a direct effect on the CD4+ T cells and triggers proliferation and can prevent anergy induction. Other cytokines, such as IFN-, can activate macrophages and natural killer (NK) cells and enhance the functional activity of CTL. In addition, IFN- can have antitumor effects by inhibiting the formation of new blood vessels in the tumour stroma.
Unlike conventional CD4+ T cells, MHC class I-restricted helper cells can recognize peptide epitopes presented by MHC class II-negative non-professional APCs. This is a critical issue as anergic class I-restricted helper T cells may inhibit ongoing antitumor immune responses and thus promote tumur growth in cancer patients. Class I-restricted helper cells activated upon peptide recognition on the surface of tumour cells may also enhance antitumor immunity in these individuals.
However, it is appealing to use monoclonal TCRs. TCRs may trigger a wide spectrum of effector functions and can have long-lasting therapeutic effects in cancer patients. The TCR approach has an advantage of no immunogenicity requirements. High-avidity TCRs are isolated readily from human T cells and can be introduced reliably into patient lymphocytes.
Article Synthesis
This review article was clearly written and easily understood. There is much value to this study in that cutting-edge therapies for cancer are discussed. Although much of the article is speculative, these ideas provide a base for future, viable therapies with a broad patient coverage. No research was performed in this manuscript. This was a review article that synthesized several key manuscripts related to the topic matter. However, the review of the pertinent literature was thorough.
Overall, the introduction of unmodified TCR genes into lymphocytes is particularly attractive because modified TCR chains may provoke immune responses and trigger rejection of injected lymphocytes, thus preventing memory development. This intervention may provide a viable treatment for cancer patients in the future.
Reference
Xue, S., Gillmore, R., Downs, a., Tsallios, a., Holler, a., Gao, L., et al. (2005). Exploiting T cell receptor genes for cancer immunotherapy. Clin Exp Immunol, 139(2), 167-172.
