WFRF:(Ramachandran Mohanraj)
Sökning: WFRF:(Ramachandran Mohanraj) > Systemic treatment ...
Systemic treatment with CAR-engineered T cells against PSCA delays subcutaneous tumor growth and prolongs survival of mice
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- Hillerdal, Victoria (författare)
- Uppsala universitet,Klinisk immunologi
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- Ramachandran, Mohanraj (författare)
- Uppsala universitet,Klinisk immunologi
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- Leja, Justyna (författare)
- Uppsala universitet,Klinisk immunologi
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- 2014-01-18
- 2014
- Engelska.
- Ingår i: BMC Cancer. - : Springer Science and Business Media LLC. - 1471-2407. ; 14, s. 30-
- Tidskriftsartikel (refereegranskat)
Abstract
Ämnesord
Stäng
- Background:Adoptive transfer of T cells genetically engineered with a chimeric antigen receptor (CAR) has successfully been used to treat both chronic and acute lymphocytic leukemia as well as other hematological cancers. Experimental therapy with CAR-engineered T cells has also shown promising results on solid tumors. The prostate stem cell antigen (PSCA) is a protein expressed on the surface of prostate epithelial cells as well as in primary and metastatic prostate cancer cells and therefore a promising target for immunotherapy of prostate cancer. Methods:We developed a third-generation CAR against PSCA including the CD28, OX-40 and CD3 zeta signaling domains. T cells were transduced with a lentivirus encoding the PSCA-CAR and evaluated for cytokine production (paired Student's t-test), proliferation (paired Student's t-test), CD107a expression (paired Student's t-test) and target cell killing in vitro and tumor growth and survival in vivo (Log-rank test comparing Kaplan-Meier survival curves).Results:PSCA-CAR T cells exhibit specific interferon (IFN)-gamma and interleukin (IL)-2 secretion and specific proliferation in response to PSCA-expressing target cells. Furthermore, the PSCA-CAR-engineered T cells efficiently kill PSCA-expressing tumor cells in vitro and systemic treatment with PSCA-CAR-engineered T cells significantly delays subcutaneous tumor growth and prolongs survival of mice.Conclusions:Our data confirms that PSCA-CAR T cells may be developed for treatment of prostate cancer.
Nyckelord
- CAR T cells
- PSCA
- Genetic engineering
- Prostate cancer
- Adoptive transfer
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- Leja, Justyna
- Essand, Magnus
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- BMC Cancer
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- Uppsala universitet
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