Tumor regression and immunity in combination therapy with anti-CEA chimeric antigen receptor T cells and anti-CEA-IL2 immunocytokine

References

• MayoClinic, Colon Cancer.
   Google Scholar
• Colon Cancer Treatment (PDQ(R)): Health Professional Version, in PDQ Cancer Information Summaries. 2002: Bethesda MD.
   Google Scholar
• Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68(6):394–14. doi:10.3322/caac.21492.
   PubMed Web of Science ®Google Scholar
• Sur D, Havasi A, Cainap C, Samasca G, Burz C, Balacescu O, Lupan I, Deleanu D, Irimie A. Chimeric antigen receptor t-cell therapy for colorectal cancer. J Clin Med. 2020;9(1):182-201. doi:10.3390/jcm9010182.
   Web of Science ®Google Scholar
• Waks AG, Winer EP. Breast cancer treatment: a review. Jama. 2019;321(3):288–300. doi:10.1001/jama.2018.19323.
   PubMed Web of Science ®Google Scholar
• Esteva FJ, Hubbard-Lucey VM, Tang J, Pusztai L. Immunotherapy and targeted therapy combinations in metastatic breast cancer. Lancet Oncol. 2019;20(3):e175–e186. doi:10.1016/S1470-2045(19)30026-9.
   PubMed Web of Science ®Google Scholar
• Gold P, Freedman SO. Demonstration of tumor-specific antigens in human colonic carcinomata by immunological tolerance and absorption techniques. J Exp Med. 1965;121(3):439–462. doi:10.1084/jem.121.3.439.
   PubMed Web of Science ®Google Scholar
• Molina R, Barak V, van Dalen A, Duffy MJ, Einarsson R, Gion M, Goike H, Lamerz R, Nap M, Sölétormos G, et al. Tumor markers in breast cancer- european group on tumor markers recommendations. Tumour Biol. 2005;26(6):281–293. doi:10.1159/000089260.
   PubMedGoogle Scholar
• Molina R, Jo J, Zanón G, Filella X, Farrus B, Muñoz M, Latre ML, Pahisa J, Velasco M, Fernandez P, et al. Utility of C-erbB-2 in tissue and in serum in the early diagnosis of recurrence in breast cancer patients: comparison with carcinoembryonic antigen and CA 15.3. Br J Cancer. 1996;74(7):1126–1131. doi:10.1038/bjc.1996.501.
   PubMed Web of Science ®Google Scholar
• Molina R, Zanón G, Filella X, Moreno F, JJ, Daniels M, Latre ML, Giménez N, Pahisa J, Velasco M, et al. Use of serial carcinoembryonic antigen and CA 15.3 assays in detecting relapses in breast cancer patients. Breast Cancer Res Treat. 1995;36(1):41–48. doi:10.1007/BF00690183.
   PubMed Web of Science ®Google Scholar
• Li X, Dai D, Chen B, Tang H, Xie X, Wei W. Determination of the prognostic value of preoperative CA15-3 and CEA in predicting the prognosis of young patients with breast cancer. Oncol Lett. 2018;16(4):4679–4688. doi:10.3892/ol.2018.9160.
   PubMed Web of Science ®Google Scholar
• Eker B, Ozaslan E, Karaca H, Berk V, Bozkurt O, Inanc M, Duran AO, Ozkan M. Factors affecting prognosis in metastatic colorectal cancer patients. Asian Pac J Cancer Prev. 2015;16(7):3015–3021. doi:10.7314/APJCP.2015.16.7.3015.
   PubMedGoogle Scholar
• Powell E, Shao J, Picon HM, Bristow C, Ge Z, Peoples M, Robinson F, Jeter-Jones SL, Schlosberg C, Grzeskowiak CL, et al. A functional genomic screen in vivo identifies CEACAM5 as a clinically relevant driver of breast cancer metastasis. NPJ Breast Cancer. 2018;4:9. doi:10.1038/s41523-018-0062-x.
   PubMed Web of Science ®Google Scholar
• Mansour EG, Hastert M, Park CH, Koehler KA, Petrelli M. Tissue and plasma carcinoembryonic antigen in early breast cancer. A prognostic factor. Cancer. 1983;51(7):1243–1248. doi:10.1002/1097-0142(19830401)51:7<1243::AID-CNCR2820510712>3.0.CO;2-A.
   PubMed Web of Science ®Google Scholar
• Pietra N, Sarli L, Costi R, Ouchemi C, Grattarola M, Peracchia A. Role of follow-up in management of local recurrences of colorectal cancer: a prospective, randomized study. Dis Colon Rectum. 1998;41(9):1127–1133. doi:10.1007/BF02239434.
   PubMed Web of Science ®Google Scholar
• Moertel CG, Fleming TR, Macdonald JS, Haller DG, Laurie JA, Tangen C. An evaluation of the carcinoembryonic antigen (CEA) test for monitoring patients with resected colon cancer. Jama. 1993;270(8):943–947. doi:10.1001/jama.1993.03510080047030.
   PubMed Web of Science ®Google Scholar
• Graham RA, Wang S, Catalano PJ, Haller DG. Postsurgical surveillance of colon cancer: preliminary cost analysis of physician examination, carcinoembryonic antigen testing, chest x-ray, and colonoscopy. Ann Surg. 1998;228(1):59–63. doi:10.1097/00000658-199807000-00009.
   PubMed Web of Science ®Google Scholar
• Woo J, Kim J, Park I, Cho H, Gwak G, Yang KH, Bae BN, Kim KH. Perioperative serum carcinoembryonic antigen ratio is a prognostic indicator in patients with stage ii colorectal cancer. Ann Coloproctol. 2018;34(1):4–10. doi:10.3393/ac.2018.34.1.4.
   PubMed Web of Science ®Google Scholar
• Lin BR, Lin YL, Lai HS, Lee PH, Chang KJ, Liang JT. Overall survival of stage III colon cancer with only one lymph node metastasis is independently predicted by preoperative carcinoembryonic antigen level and lymph node sampling status. PLoS One. 2015;10(9):e0137053. doi:10.1371/journal.pone.0137053.
   PubMed Web of Science ®Google Scholar
• Duffy MJ. Carcinoembryonic antigen as a marker for colorectal cancer: is it clinically useful? Clin Chem. 2001;47(4):624–630. doi:10.1093/clinchem/47.4.624.
   PubMed Web of Science ®Google Scholar
• Duffy MJ, van Dalen A, Haglund C, Hansson L, Klapdor R, Lamerz R, Nilsson O, Sturgeon C, Topolcan O. Clinical utility of biochemical markers in colorectal cancer: European group on tumour markers (EGTM) guidelines. Eur J Cancer. 2003;39(6):718–727. doi:10.1016/S0959-8049(02)00811-0.
   PubMed Web of Science ®Google Scholar
• Shousha S, Lyssiotis T, Godfrey VM, Scheuer PJ. Carcinoembryonic antigen in breast-cancer tissue: a useful prognostic indicator. Br Med J. 1979;1(6166):777–779. doi:10.1136/bmj.1.6166.777.
   PubMed Web of Science ®Google Scholar
• Ordonez C, Screaton RA, Ilantzis C, Stanners CP. Human carcinoembryonic antigen functions as a general inhibitor of anoikis. Cancer Res. 2000;60(13):3419–3424.
   PubMed Web of Science ®Google Scholar
• Li L, Bading J, Yazaki PJ, Ahuja AH, Crow D, Colcher D, Williams LE, Wong JYC, Raubitschek A, Shively JE. A versatile bifunctional chelate for radiolabeling humanized anti-CEA antibody with In-111 and Cu-64 at either thiol or amino groups: PET imaging of CEA-positive tumors with whole antibodies. Bioconjug Chem. 2008;19(1):89–96. doi:10.1021/bc700161p.
   PubMed Web of Science ®Google Scholar
• Wong JY, Chu DZ, Williams LE, Liu A, Zhan J, Yamauchi DM, Wilczynski S, Wu AM, Yazaki PJ, Shively JE. A phase I trial of (90)Y-DOTA-anti-CEA chimeric T84.66 (cT84.66) radioimmunotherapy in patients with metastatic CEA-producing malignancies. Cancer Biother Radiopharm. 2006;21(2):88–100. doi:10.1089/cbr.2006.21.88.
   PubMed Web of Science ®Google Scholar
• Wong JYC, Williams LE, Yamauchi DM, Odom-Maryon T, Esteban JM, Neumaier M, Wu AM, Johnson DK, Primus FJ, Shively JE, et al. Initial experience evaluating 90yttrium-radiolabeled anti-carcinoembryonic antigen chimeric T84.66 in a phase I radioimmunotherapy trial. Cancer Res. 1995;55(23 Supplement):5929s–5934s.
   PubMed Web of Science ®Google Scholar
• Schlom J. Basic principles and applications of monoclonal antibodies in the management of carcinomas: the richard and hinda rosenthal foundation award lecture. Cancer Res. 1986;46:3225–3238.
   PubMed Web of Science ®Google Scholar
• Kuroki M, Kuroki M, Koga Y, Matsuoka Y. Monoclonal antibodies to carcinoembryonic antigen: a systematic analysis of antibody specificities by using related normal antigens and evidence for allotypic determinants on carcinoembryonic antigen. J Immunol. 1984;133(4):2090–2097.
   PubMed Web of Science ®Google Scholar
• Lonberg N, Taylor LD, Harding FA, Trounstine M, Higgins KM, Schramm SR, Kuo CC, Mashayekh R, Wymore K, McCabe JG, et al. Antigen-specific human antibodies from mice comprising four distinct genetic modifications. Nature. 1994;368(6474):856–859. doi:10.1038/368856a0.
   PubMed Web of Science ®Google Scholar
• Primus FJ, Newell KD, Blue A, Goldenberg DM. Immunological heterogeneity of carcinoembryonic antigen: antigenic determinants on carcinoembryonic antigen distinguished by monoclonal antibodies. Cancer Res. 1983;43(2):686–692.
   PubMed Web of Science ®Google Scholar
• Fesnak AD, June CH, Levine BL. Engineered T cells: the promise and challenges of cancer immunotherapy. Nat Rev Cancer. 2016;16:566–581.
   PubMed Web of Science ®Google Scholar
• Chmielewski M, Hahn O, Rappl G, Nowak M, Schmidt-Wolf IH, Hombach AA, Abken H. T cells that target carcinoembryonic antigen eradicate orthotopic pancreatic carcinomas without inducing autoimmune colitis in mice. Gastroenterology. 2012;143(4):1095–1107. e2. doi:10.1053/j.gastro.2012.06.037.
   PubMed Web of Science ®Google Scholar
• Katz SC, Burga RA, McCormack E, Wang LJ, Mooring W, Point GR, Khare PD, Thorn M, Ma Q, Stainken BF, et al. Phase I hepatic immunotherapy for metastases study of intra-arterial chimeric antigen receptor-modified T-cell therapy for CEA+ liver metastases. Clin Cancer Res. 2015;21(14):3149–3159. doi:10.1158/1078-0432.CCR-14-1421.
   PubMed Web of Science ®Google Scholar
• Kujawski M, Burga RA, McCormack E, Wang LJ, Mooring W, Point GR, Khare PD, Thorn M, Ma Q, Stainken BF et al. Potent immunomodulatory effects of an anti-CEA-IL-2 immunocytokine on tumor therapy and effects of stereotactic radiation. OncoImmunology. 2020;9(1):1724052. doi:10.1080/2162402X.2020.1724052.
   PubMed Web of Science ®Google Scholar
• He Z, Ma J, Wang R, Zhang J, Huang Z, Wang F, Sen S, Rothenberg EV, Sun Z. A two-amino-acid substitution in the transcription factor RORgammat disrupts its function in TH17 differentiation but not in thymocyte development. Nat Immunol. 2017;18(10):1128–1138. doi:10.1038/ni.3832.
   PubMed Web of Science ®Google Scholar
• Neumaier M, Shively L, Chen FS, Gaida FJ, Ilgen C, Paxton RJ, Shively JE. Cloning of the genes for T84.66, an antibody that has a high specificity and affinity for carcinoembryonic antigen, and expression of chimeric human/mouse T84.66 genes in myeloma and Chinese hamster ovary cells. Cancer Res. 1990;50(7):2128–2134.
   PubMed Web of Science ®Google Scholar
• Murad JP, Kozlowska AK, Lee HJ, Ramamurthy M, Chang WC, Yazaki P, Colcher D, Shively J, Cristea M, Forman SJ, et al. Effective targeting of TAG72(+) peritoneal ovarian tumors via regional delivery of CAR-engineered t cells. Front Immunol. 2018;9:2268. doi:10.3389/fimmu.2018.02268.
   PubMed Web of Science ®Google Scholar
• Brown CE, Aguilar B, Starr R, Yang X, Chang W-C, Weng L, Chang B, Sarkissian A, Brito A, Sanchez JF, et al. Optimization of IL13Rα2-targeted chimeric antigen receptor T cells for improved anti-tumor efficacy against glioblastoma. Molecular Therapy. 2018;26(1):31–44. doi:10.1016/j.ymthe.2017.10.002.
   PubMed Web of Science ®Google Scholar
• Priceman SJ, Tilakawardane D, Jeang B, Aguilar B, Murad JP, Park AK, Chang WC, Ostberg JR, Neman J, Jandial R, et al. Regional delivery of chimeric antigen receptor-engineered T cells effectively targets HER2(+) breast cancer metastasis to the brain. Clin Cancer Res. 2018;24(1):95–105. doi:10.1158/1078-0432.CCR-17-2041.
   PubMed Web of Science ®Google Scholar
• Donnelly MLL, Luke G, Mehrotra A, Li X, Hughes LE, Gani D, Ryan MD. Analysis of the aphthovirus 2A/2B polyprotein ‘cleavage’ mechanism indicates not a proteolytic reactionbut a novel translational effect: a putative ribosomal ‘skip’. J Gen Virol. 2001;82(Pt 5):1013–1025.
   PubMed Web of Science ®Google Scholar
• Clarke P,Mann J, Simpson JF, Rickard-Dickson K, Primus FJ.  Mice transgenic for human carcinoembryonic antigen as a model for immunotherapy. Cancer Res. 1998;58(7):1469–1477.
   PubMed Web of Science ®Google Scholar
• Yazaki PJ, Wu AM, Tsai SW, Williams LE, Ikle DN, Wong JYC, Shively JE, Raubitschek AA. Tumor targeting of radiometal labeled anti-cea recombinant t84.66 diabody and t84.66 minibody: Comparison to radioiodinated fragments. Bioconjug Chem. 2001;12(2):220–228. doi:10.1021/bc000092h.
   PubMed Web of Science ®Google Scholar
• Crouch ML,Knowels G, Stuppard R, Ericson NG, Bielas JH, Marcinek DJ, Syrjala KL. Cyclophosphamide leads to persistent deficits in physical performance and in vivo mitochondria function in a mouse model of chemotherapy late effects. PLoS One. 2017;12(7):e0181086. doi:10.1371/journal.pone.0181086.
   PubMed Web of Science ®Google Scholar
• Jafarzadeh L,Masoumi E, Fallah-Mehrjardi K, Mirzaei HR, Hadjati J. Prolonged persistence of chimeric antigen receptor (CAR) T cell in adoptive cancer immunotherapy: Challenges and ways forward. Front Immunol. 2020;11:702. doi:10.3389/fimmu.2020.00702.
   PubMed Web of Science ®Google Scholar
• Gattinoni L, Finkelstein SE, Klebanoff CA, Antony PA, Palmer DC, Spiess PJ, Hwang LN, Yu Z, Wrzesinski C, Heimann DM, et al. Removal of homeostatic cytokine sinks by lymphodepletion enhances the efficacy of adoptively transferred tumor-specific CD8+ T cells. J Exp Med. 2005;202(7):907–912. doi:10.1084/jem.20050732.
   PubMed Web of Science ®Google Scholar
• Bracci L, oschella F, Sestili P, La Sorsa V, Valentini M, Canini I, Baccarini S, Maccari S, Ramoni C, Belardelli F, et al. Cyclophosphamide enhances the antitumor efficacy of adoptively transferred immune cells through the induction of cytokine expression, B-cell and T-cell homeostatic proliferation, and specific tumor infiltration. Clin Cancer Res. 2007;13(2 Pt 1):644–653. doi:10.1158/1078-0432.CCR-06-1209.
   PubMed Web of Science ®Google Scholar
• Xu J, Wang Y, Shi J, Liu J, Li Q, Chen L. Combination therapy: a feasibility strategy for CAR-T cell therapy in the treatment of solid tumors. Oncol Lett. 2018;16(2):2063–2070. doi:10.3892/ol.2018.8946.
   PubMed Web of Science ®Google Scholar
• Vierboom MP,Bos GM, Ooms M, Offringa R, Melief CJ. Cyclophosphamide enhances anti-tumor effect of wild-type p53-specific CTL. Int J Cancer. 2000;87(2):253–260. doi:10.1002/1097-0215(20000715)87:2<253::AID-IJC17>3.0.CO;2-A.
   PubMed Web of Science ®Google Scholar
• Alizadeh D,Trad M, Hanke NT, Larmonier CB, Janikashvili N, Bonnotte B, Katsanis E, Larmonier N. Doxorubicin eliminates myeloid-derived suppressor cells and enhances the efficacy of adoptive T-cell transfer in breast cancer. Cancer Res. 2014;74(1):104–118. doi:10.1158/0008-5472.CAN-13-1545.
   PubMed Web of Science ®Google Scholar
• Peng KW,Myers R, Greenslade A, Mader E, Greiner S, Federspiel MJ, Dispenzieri A, Russell SJ. Using clinically approved cyclophosphamide regimens to control the humoral immune response to oncolytic viruses. Gene Ther. 2013;20(3):255–261. doi:10.1038/gt.2012.31.
   PubMed Web of Science ®Google Scholar
• Lutsiak ME,Semnani RT, De Pascalis R, Kashmiri SV, Schlom J, Sabzevari H. Inhibition of CD4(+)25+ T regulatory cell function implicated in enhanced immune response by low-dose cyclophosphamide. Blood. 2005;105(7):2862–2868. doi:10.1182/blood-2004-06-2410.
   PubMed Web of Science ®Google Scholar
• Myers CE,Hoelzinger DB, Truong TN, Chew LA, Myles A, Chaudhuri L, Egan JB, Liu J, Gendler SJ, Cohen PA. Chemotherapy can induce weight normalization of morbidly obese mice despite undiminished ingestion of high fat diet. Oncotarget. 2017;8(3):5426–5438. doi:10.18632/oncotarget.14576.
   PubMedGoogle Scholar
• Eftekhar E, Naghibalhossaini F. Carcinoembryonic antigen expression level as a predictive factor for response to 5-fluorouracil in colorectal cancer. Mol Biol Rep. 2014;41(1):459–466. doi:10.1007/s11033-013-2880-0.
   PubMed Web of Science ®Google Scholar
• Majzner RG, Mackall CL. Tumor antigen escape from CAR T-cell therapy. Cancer Discov. 2018;8(10):1219–1226.
   Google Scholar
• Maude SL, Teachey DT, Rheingold SR, Shaw PA, Aplenc R, Barrett DM, Barker CS, Callahan C, Frey NV, Nazimuddin F, et al. 2016. Sustained remissions with CD19-specific chimeric antigen receptor (CAR)-modified T cells in children with relapsed/refractory ALL. Vol. 34( 15_suppl): 3011.
   Google Scholar
• Sotillo E, Barrett DM, Black KL, Bagashev A, Oldridge D, Wu G, Sussman R, Lanauze C, Ruella M, Gazzara MR, et al. Convergence of acquired mutations and alternative splicing of CD19 enables resistance to CART-19 immunotherapy. Cancer Discov. 2015;5(12):1282–1295. doi:10.1158/2159-8290.CD-15-1020.
   PubMed Web of Science ®Google Scholar
• Orlando EJ, Han X, Tribouley C, Wood PA, Leary RJ, Riester M, Levine JE, Qayed M, Grupp SA, Boyer M, et al. Genetic mechanisms of target antigen loss in CAR19 therapy of acute lymphoblastic leukemia. Nat Med. 2018;24(10):1504–1506. doi:10.1038/s41591-018-0146-z.
   PubMed Web of Science ®Google Scholar
• Shalabi H, Kraft IL, Wang HW, Yuan CM, Yates B, Delbrook C, Zimbelman JD, Giller R, Stetler-Stevenson M, Jaffe ES, et al. Sequential loss of tumor surface antigens following chimeric antigen receptor T-cell therapies in diffuse large B-cell lymphoma. Haematologica. 2018;103(5):e215–e218. e215-e218. doi:10.3324/haematol.2017.183459.
   PubMed Web of Science ®Google Scholar
• Qin H, Dong Z, Wang X, Cheng WA, Wen F, Xue W, Sun H, Walter M, Wei G, Smith DL, et al. CAR T cells targeting BAFF-R can overcome CD19 antigen loss in B cell malignancies. Sci Transl Med. 2019;11(511):eaaw9414. doi:10.1126/scitranslmed.aaw9414.
   PubMed Web of Science ®Google Scholar
• Klein C, Waldhauer I, Nicolini VG, Freimoser-Grundschober A, Nayak T, Vugts DJ, Dunn C, Bolijn M, Benz J, Stihle M, et al. Cergutuzumab amunaleukin (CEA-IL2v), a CEA-targeted IL-2 variant-based immunocytokine for combination cancer immunotherapy: overcoming limitations of aldesleukin and conventional IL-2-based immunocytokines. Oncoimmunology. 2017;6(3):e1277306. doi:10.1080/2162402X.2016.1277306.
   PubMed Web of Science ®Google Scholar
• Ribba B, Boetsch C, Nayak T, Grimm HP, Charo J, Evers S, Klein C, Tessier J, Charoin JE, Phipps A, et al. Prediction of the optimal dosing regimen using a mathematical model of tumor uptake for immunocytokine-based cancer immunotherapy. Clin Cancer Res. 2018;24(14):3325–3333. doi:10.1158/1078-0432.CCR-17-2953.
   PubMed Web of Science ®Google Scholar
• Van Brummelen EMJ, Huisman MC, de Wit-van der Veen LJ, Nayak TK, Stokkel MPM, Mulder ER, Hoekstra OS, Vugts DJ, Van Dongen G, Verheul HM, et al. (89)Zr-labeled CEA-targeted IL-2 variant immunocytokine in patients with solid tumors: CEA-mediated tumor accumulation and role of IL-2 receptor-binding. Oncotarget. 2018;9(37):24737–24749. doi:10.18632/oncotarget.25343.
   PubMedGoogle Scholar
• Shively JE, Beatty JD. CEA-related antigens: molecular biology and clinical significance. Crit Rev Oncol Hematol. 1985;2:355–399.
   PubMed Web of Science ®Google Scholar
• Hammarstrom S. The carcinoembryonic antigen (CEA) family: structures, suggested functions and expression in normal and malignant tissues. Semin Cancer Biol. 1999;9(2):67–81. doi:10.1006/scbi.1998.0119.
   PubMed Web of Science ®Google Scholar
• Coutelier JP, Godfraind C, Dveksler GS, Wysocka M, Cardellichio CB, Noël H, Holmes KV. B lymphocyte and macrophage expression of carcinoembryonic antigen-related adhesion molecules that serve as receptors for murine coronavirus. Eur J Immunol. 1994;24(6):1383–1390. doi:10.1002/eji.1830240622.
   PubMed Web of Science ®Google Scholar
• Kammerer R, Hahn S, Singer BB, Luo JS, von Kleist S. Biliary glycoprotein (CD66a), a cell adhesion molecule of the immunoglobulin superfamily, on human lymphocytes: structure expression and involvement in T cell activation. Eur J Immunol. 1998;28(11):3664–3674.
   PubMed Web of Science ®Google Scholar
• Tchoupa AK, Schuhmacher T, Hauck CR. Signaling by epithelial members of the CEACAM family - mucosal docking sites for pathogenic bacteria. Cell Commun Signal. 2014;12(1):27. doi:10.1186/1478-811X-12-27.
   PubMed Web of Science ®Google Scholar
• Katz SC, Point GR, Cunetta M, Thorn M, Guha P, Espat NJ, Boutros C, Hanna N, Junghans RP. Regional CAR-T cell infusions for peritoneal carcinomatosis are superior to systemic delivery. Cancer Gene Ther. 2016;23(5):142–148. doi:10.1038/cgt.2016.14.
   PubMed Web of Science ®Google Scholar
• SorrentoTherapeutics I. Sorrento Therapeutics anti-CEA CAR-t demonstrates promising clinical activity and safety in phase Ib clinical trial. 2017.
   Google Scholar
• SorrentoTherapeutics I. Sorrento therapeutics autologous anti-CEA CAR-T cell therapy for liver metastases demonstrates therapeutic activity in stage iv pancreas cancer in a phase 1b HITM-SURE Trial (NCT02850536). GlobeNewswire; 2018.
   Google Scholar
• Lo AS, Lo AS, Ma Q, Liu DL, Junghans RP. Anti-GD3 chimeric sFv-CD28/T-cell receptor zeta designer T cells for treatment of metastatic melanoma and other neuroectodermal tumors. Clin Cancer Res. 2010;16(10):2769–2780. doi:10.1158/1078-0432.CCR-10-0043.
   PubMed Web of Science ®Google Scholar
• Junghans RP, Ma Q, Rathore R, Gomes EM, Bais AJ, Lo ASY, Abedi M, Davies RA, Cabral HJ, Al-Homsi AS, et al. Phase I Trial of Anti-PSMA Designer CAR-T Cells in Prostate Cancer: possible Role for Interacting Interleukin 2-T Cell Pharmacodynamics as a Determinant of Clinical Response. Prostate. 2016;76(14):1257–1270.
   Google Scholar
• Chmielewski M, Abken H. CAR T cells releasing IL-18 Convert to T-Bet(high) FoxO1(low) effectors that exhibit augmented activity against advanced solid tumors. Cell Rep. 2017;21(11):3205–3219. doi:10.1016/j.celrep.2017.11.063.
   PubMed Web of Science ®Google Scholar
• Wagener C, Clark BR, Rickard KJ, Shively JE. Monoclonal antibodies for carcinoembryonic antigen and related antigens as a model system: determination of affinities and specificities of monoclonal antibodies by using biotin-labeled antibodies and avidin as precipitating agent in a solution phase immunoassay. J Immunol. 1983;130(5):2302–2307.
   PubMed Web of Science ®Google Scholar
• Esteban JM, Felder B, Ahn C, Simpson JF, Battifora H, Shively JE. Prognostic relevance of carcinoembryonic antigen and estrogen receptor status in breast cancer patients. Cancer. 1994;74(5):1575–1583. doi:10.1002/1097-0142(19940901)74:5<1575::aid-cncr2820740513>3.0.co;2-w.
   PubMed Web of Science ®Google Scholar
• Shively JE,  Spayth V, Chang FF, Metter GE, Klein L, Presant CA, Todd CW. Serum levels of carcinoembryonic antigen and a tumor-extracted carcinoembryonic antigen-related antigen in cancer patients. Cancer Res. 1982;42(6):2506.
   PubMed Web of Science ®Google Scholar
• Beatty JD, Duda RB, Williams LE, Sheibani K, Paxton RJ, Beatty BG, Philben VJ, Werner JL, Shively JE, Vlahos WG, et al. Preoperative imaging of colorectal carcinoma with 111in-labeled anticarcinoembryonic antigen monoclonal antibody. Cancer Res. 1986;46(12 Part 1):6494–6502.
   PubMed Web of Science ®Google Scholar
• Yazaki PJ, Lee B, Channappa D, Cheung CW, Crow D, Chea J, Poku E, Li L, Andersen JT, Sandlie I, et al. A series of anti-CEA/anti-DOTA bispecific antibody formats evaluated for pre-targeting: comparison of tumor uptake and blood clearance. Protein Eng Des Sel. 2013;26(3):187–193. doi:10.1093/protein/gzs096.
   PubMed Web of Science ®Google Scholar
• Nittka S,  Krueger MA, Shively JE, Boll H, Brockmann MA, Doyon F, Pichler BJ, Neumaier M. Radioimmunoimaging of liver metastases with PET using a 64Cu-labeled CEA antibody in transgenic mice. PLoS One. 2014;9(9):e106921. doi:10.1371/journal.pone.0106921.
   PubMed Web of Science ®Google Scholar
• Wu AM, Yazaki PJ, Tsai S, Nguyen K, Anderson AL, McCarthy DW, Welch MJ, Shively JE, Williams LE, Raubitschek AA, et al. High-resolution microPET imaging of carcinoembryonic antigen-positive xenografts by using a copper-64-labeled engineered antibody fragment. Proc Natl Acad Sci U S A. 2000;97(15):8495–8500. doi:10.1073/pnas.150228297.
   PubMed Web of Science ®Google Scholar
• Parkhurst MR, Yang JC, Langan RC, Dudley ME, Nathan DA, Feldman SA, Davis JL, Morgan RA, Merino MJ, Sherry RM, et al. T cells targeting carcinoembryonic antigen can mediate regression of metastatic colorectal cancer but induce severe transient colitis. Mol Ther. 2011;19(3):620–626. doi:10.1038/mt.2010.272.
   PubMed Web of Science ®Google Scholar
• Dudley ME, Wunderlich JR, Robbins PF, Yang JC, Hwu P, Schwartzentruber DJ, Topalian SL, Sherry R, Restifo NP, Hubicki AM, et al. Cancer regression and autoimmunity in patients after clonal repopulation with antitumor lymphocytes. Science. 2002;298(5594):850–854. doi:10.1126/science.1076514.
   PubMed Web of Science ®Google Scholar
• Robbins PF, Dudley ME, Wunderlich J, El-Gamil M, Li YF, Zhou J, Huang J, Powell DJ, Jr., Rosenberg SA. Cutting edge: persistence of transferred lymphocyte clonotypes correlates with cancer regression in patients receiving cell transfer therapy. J Immunol. 2004;173(12):7125–7130. doi:10.4049/jimmunol.173.12.7125.
   PubMed Web of Science ®Google Scholar
• Hege KM, Bergsland EK, Fisher GA, Nemunaitis JJ, Warren RS, McArthur JG, Lin AA, Schlom J, June CH, Sherwin SA. Safety, tumor trafficking and immunogenicity of chimeric antigen receptor (CAR)-T cells specific for TAG-72 in colorectal cancer. J Immunother Cancer. 2017;5(1):22. doi:10.1186/s40425-017-0222-9.
   PubMed Web of Science ®Google Scholar
• Wu J, Waxman DJ. Metronomic cyclophosphamide eradicates large implanted GL261 gliomas by activating antitumor Cd8(+) T-cell responses and immune memory. Oncoimmunology. 2015;4(4):e1005521. doi:10.1080/2162402X.2015.1005521.
   PubMed Web of Science ®Google Scholar