TY - JOUR
T1 - Prospects for gene-engineered T cell immunotherapy for solid cancers
AU - Klebanoff, Christopher A.
AU - Rosenberg, Steven A.
AU - Restifo, Nicholas P.
N1 - Funding Information:
This work was supported by the Intramural Research Program of the National Cancer Institute, Center for Cancer Research of the US National Institutes of Health (NIH) (ZIA BC011586 and ZIA BC010763) and the NIH Center for Regenerative Medicine. Additional support was provided by generous gifts from L. Jinyuan of the Tiens Charitable Foundation and the Milstein Family Foundation.
PY - 2016/1/6
Y1 - 2016/1/6
N2 - Adoptive transfer of receptor-engineered T cells has produced impressive results in treating patients with B cell leukemias and lymphomas. This success has captured public imagination and driven academic and industrial researchers to develop similar 'off-the-shelf' receptors targeting shared antigens on epithelial cancers, the leading cause of cancer-related deaths. However, the successful treatment of large numbers of people with solid cancers using this strategy is unlikely to be straightforward. Receptor-engineered T cells have the potential to cause lethal toxicity from on-target recognition of normal tissues, and there is a paucity of truly tumor-specific antigens shared across tumor types. Here we offer our perspective on how expanding the use of genetically redirected T cells to treat the majority of patients with solid cancers will require major technical, manufacturing and regulatory innovations centered around the development of autologous gene therapies targeting private somatic mutations.
AB - Adoptive transfer of receptor-engineered T cells has produced impressive results in treating patients with B cell leukemias and lymphomas. This success has captured public imagination and driven academic and industrial researchers to develop similar 'off-the-shelf' receptors targeting shared antigens on epithelial cancers, the leading cause of cancer-related deaths. However, the successful treatment of large numbers of people with solid cancers using this strategy is unlikely to be straightforward. Receptor-engineered T cells have the potential to cause lethal toxicity from on-target recognition of normal tissues, and there is a paucity of truly tumor-specific antigens shared across tumor types. Here we offer our perspective on how expanding the use of genetically redirected T cells to treat the majority of patients with solid cancers will require major technical, manufacturing and regulatory innovations centered around the development of autologous gene therapies targeting private somatic mutations.
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U2 - 10.1038/nm.4015
DO - 10.1038/nm.4015
M3 - Review article
C2 - 26735408
AN - SCOPUS:84954236800
SN - 1078-8956
VL - 22
SP - 26
EP - 36
JO - Nature medicine
JF - Nature medicine
IS - 1
ER -