Abstract
Adoptive T-cell therapy is based on specificity and efficacy, two essentials known to be necessary for successful cancer therapy. Tumor-reactive T-cells potentially display both characteristics in terms of antigen recognition and antitumor activity. In recent years, novel technologies have been established for the identification, isolation, activation, and expansion of human T-cells, which have greatly facilitated the further development of adoptive T-cell transfer regimens. Lessons learned from the first clinical trials revealed that the complexity of the in vivo environment interferes with the efficacy of transferred T-cells, such as tolerance induction and outgrowth of tumor escape variants. The results from these studies can be concluded by the following critical, but nevertheless encouraging, statement: “Tumor regressions observed after adoptive Tcell transfer are too frequent to be spontaneous.” As these trials are not solely conducted for treating cancer patients, but also for research on human beings, the resulting scientific observations have increased our understanding of T-cell activation, homing, and survival, as well as of the possibility of disrupting regulatory mechanisms. The knowledge drawn from the first generation of transfer studies can be implemented in the next generation of clinical trials. T-cell-based immunotherapy regimens are currently being combined with other immunological strategies in order to coordinate an effective attack against tumors. Further development of combinatorial therapies involving immunological and molecular technologies will offer the means to tailor adoptive transfer of T-cell immunity for each cancer patient.
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Bernhard, H., Neudorfer, J., Gebhard, K., Conrad, H., Busch, D.H., Peschel, C. (2006). Tumor-Reactive T-Cells for Adoptive Immunotherapy. In: Disis, M.L. (eds) Immunotherapy of Cancer. Cancer Drug Discovery and Development. Humana Press. https://doi.org/10.1385/1-59745-011-1:167
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