TY - JOUR
T1 - Acquired erythropoietin responsiveness of interleukin-2-dependent T lymphocytes retrovirally transduced with genes encoding chimeric erythropoietin/interleukin-2 receptors
AU - Minamoto, Seijiro
AU - Treisman, Jonathan
AU - Hankins, W. David
AU - Sugamura, Kazuo
AU - Rosenberg, Steven A.
PY - 1995/9/15
Y1 - 1995/9/15
N2 - Adoptive immunotherapy with tumor-infiltrating lymphocytes (TILs) causes regression of some human tumors. However, the sustained proliferation and antitumor activity of TILs requires the coadministration of potentially toxic amounts of interleukin-2 (IL-2). In an effort to overcome the requirement by T cells for IL-2, we have introduced alternative growth factor receptors that use the relatively nontoxic cytokine erythropoietin (Epo) as a ligand. In our model system, the coexpression of chimeric receptors consisting of the extracellular portion of the Epo receptor (EpoR) and the intracellular portions of the IL-2 receptor subunits, β and γ, conferred Epo responsiveness on a T-cell line. By contrast, cells expressing the wild-type EpoR did not proliferate in response to Epo. This suggested that Epo binding caused the activation of an IL-2 signal pathway mediated by the chimeric receptors. This approach can be used to minimize toxicity and potentially improve cancer immunotherapy with TILs.
AB - Adoptive immunotherapy with tumor-infiltrating lymphocytes (TILs) causes regression of some human tumors. However, the sustained proliferation and antitumor activity of TILs requires the coadministration of potentially toxic amounts of interleukin-2 (IL-2). In an effort to overcome the requirement by T cells for IL-2, we have introduced alternative growth factor receptors that use the relatively nontoxic cytokine erythropoietin (Epo) as a ligand. In our model system, the coexpression of chimeric receptors consisting of the extracellular portion of the Epo receptor (EpoR) and the intracellular portions of the IL-2 receptor subunits, β and γ, conferred Epo responsiveness on a T-cell line. By contrast, cells expressing the wild-type EpoR did not proliferate in response to Epo. This suggested that Epo binding caused the activation of an IL-2 signal pathway mediated by the chimeric receptors. This approach can be used to minimize toxicity and potentially improve cancer immunotherapy with TILs.
UR - http://www.scopus.com/inward/record.url?scp=0029134822&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0029134822&partnerID=8YFLogxK
U2 - 10.1182/blood.v86.6.2281.bloodjournal8662281
DO - 10.1182/blood.v86.6.2281.bloodjournal8662281
M3 - Article
C2 - 7662975
AN - SCOPUS:0029134822
SN - 0006-4971
VL - 86
SP - 2281
EP - 2287
JO - Blood
JF - Blood
IS - 6
ER -