Chimeric NKG2D receptor–bearing T cells as immunotherapy for ovarian cancer
A Barber, T Zhang, LR DeMars, J Conejo-Garcia… - Cancer research, 2007 - AACR
A Barber, T Zhang, LR DeMars, J Conejo-Garcia, KF Roby, CL Sentman
Cancer research, 2007•AACRDespite advancements in the treatment of ovarian cancer, this disease continues to be a
leading cause of cancer death in women. Adoptive transfer of tumor-reactive T cells is a
promising antitumor therapy for many cancers. We designed a chimeric receptor linking
NKG2D, a natural killer (NK) cell–activating receptor, to the CD3ζ chain of the T-cell receptor
to target ovarian tumor cells. Engagement of chimeric NKG2D receptors (chNKG2D) with
ligands for NKG2D, which are commonly expressed on tumor cells, leads to T-cell secretion …
leading cause of cancer death in women. Adoptive transfer of tumor-reactive T cells is a
promising antitumor therapy for many cancers. We designed a chimeric receptor linking
NKG2D, a natural killer (NK) cell–activating receptor, to the CD3ζ chain of the T-cell receptor
to target ovarian tumor cells. Engagement of chimeric NKG2D receptors (chNKG2D) with
ligands for NKG2D, which are commonly expressed on tumor cells, leads to T-cell secretion …
Abstract
Despite advancements in the treatment of ovarian cancer, this disease continues to be a leading cause of cancer death in women. Adoptive transfer of tumor-reactive T cells is a promising antitumor therapy for many cancers. We designed a chimeric receptor linking NKG2D, a natural killer (NK) cell–activating receptor, to the CD3ζ chain of the T-cell receptor to target ovarian tumor cells. Engagement of chimeric NKG2D receptors (chNKG2D) with ligands for NKG2D, which are commonly expressed on tumor cells, leads to T-cell secretion of proinflammatory cytokines and tumor cytotoxicity. In this study, we show that >80% of primary human ovarian cancer samples expressed ligands for NKG2D on the cell surface. The tumor samples expressed MHC class I–related protein A, MICB, and UL-16 binding proteins 1 and 3. ChNKG2D-expressing T cells lysed ovarian cancer cell lines. We show that T cells from ovarian cancer patients that express chNKG2D secreted proinflammatory cytokines when cultured with autologous tumor cells. In addition, we show that chNKG2D T cells can be used therapeutically in a murine model of ovarian cancer. These data indicate that treatment with chNKG2D-expressing T cells is a potential immunotherapy for ovarian cancer. [Cancer Res 2007;67(10):5003–8]
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