RT Journal Article
SR Electronic
T1 Mesothelin-Specific Chimeric Antigen Receptor mRNA-Engineered T Cells Induce Antitumor Activity in Solid Malignancies
JF Cancer Immunology Research
JO Cancer Immunol Res
FD American Association for Cancer Research
SP 112
OP 120
DO 10.1158/2326-6066.CIR-13-0170
VO 2
IS 2
A1 Beatty, Gregory L.
A1 Haas, Andrew R.
A1 Maus, Marcela V.
A1 Torigian, Drew A.
A1 Soulen, Michael C.
A1 Plesa, Gabriela
A1 Chew, Anne
A1 Zhao, Yangbing
A1 Levine, Bruce L.
A1 Albelda, Steven M.
A1 Kalos, Michael
A1 June, Carl H.
YR 2014
UL http://cancerimmunolres.aacrjournals.org/content/2/2/112.abstract
AB Off-target toxicity due to the expression of target antigens in normal tissue represents a major obstacle to the use of chimeric antigen receptor (CAR)-engineered T cells for treatment of solid malignancies. To circumvent this issue, we established a clinical platform for engineering T cells with transient CAR expression by using in vitro transcribed mRNA encoding a CAR that includes both the CD3-ζ and 4-1BB costimulatory domains. We present two case reports from ongoing trials indicating that adoptive transfer of mRNA CAR T cells that target mesothelin (CARTmeso cells) is feasible and safe without overt evidence of off-tumor on-target toxicity against normal tissues. CARTmeso cells persisted transiently within the peripheral blood after intravenous administration and migrated to primary and metastatic tumor sites. Clinical and laboratory evidence of antitumor activity was shown in both patients, and the CARTmeso cells elicited an antitumor immune response revealed by the development of novel antiself antibodies. These data show the potential of using mRNA-engineered T cells to evaluate, in a controlled manner, potential off-tumor on-target toxicities and show that short-lived CAR T cells can induce epitope spreading and mediate antitumor activity in patients with advanced cancer. Thus, these findings support the development of mRNA CAR-based strategies for carcinoma and other solid tumors. Cancer Immunol Res; 2(2); 112–20. ©2013 AACR.