The recent achievement of durable engraftment of adoptively transferred T cells endowed with a CAR and costimulatory molecule provides an extraordinary opportunity to implement novel immunotherapies for cancer and to define the principles required for eradicating both hematopoietic malignancies and solid tumors. Advances in methods for selection of T cells with defined characteristics, T-cell stimulation and culture, genetic engineering and nanotechnology are likely to further improve the potency of T-cell therapy and allow investigators to dissect at high resolution the in vivo interactions between engineered tumor-reactive T cells and tumor cells in the tumor microenvironment. The development of more favorable allogeneic HCT platforms for transferring donor tumor-reactive T cells remains an unmet challenge that must be overcome to improve the use of adoptive therapy in this setting.
As the efficacy of T-cell therapy improves, so too will the risk of on-target toxicity, mandating the discovery of novel tumor-specific antigens and development of rapidly effective strategies for regulating tumor cell recognition by transferred T cells either by elimination of infused cells or controlling expression of tumor targeting receptors. Finally, collaboration should be a focus of future investigation so that formal evaluation of new therapies can be accomplished rapidly and in appropriately designed clinical trials.
The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute or the NIH.
Expert Rev Hematol. 2012;5(4):409-425. © 2012 Expert Reviews Ltd.