Login Register Cart 0
Generic placeholder image

Current Cancer Drug Targets

Editor-in-Chief

ISSN (Print): 1568-0096
ISSN (Online): 1873-5576

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

CT109-SN-38, a Novel Antibody-drug Conjugate with Dual Specificity for CEACAM5 and 6, Elicits Potent Killing of Pancreatic Cancer Cells

Author(s): Kelly C. Arias Cardenas, Clinton W. Enos, Mark R. Spear*, Dana E. Austin, Raghad Almofeez, Stephanie Kortchak, Lauren Pincus, Hua-bei Guo, Samuel Dolezal, J. Michael Pierce, Emma Furth, Cyrille Gineste, Yongjun Kwon and Cohava Gelber

Volume 24, Issue 7, 2024

Published on: 04 January, 2024

Page: [720 - 732] Pages: 13

DOI: 10.2174/0115680096260614231115192343

Price: $65

Abstract

Background: CEACAM5 and CEACAM6 are glycosylphosphatidylinositol (GPI)- linked members of the carcinoembryonic antigen-related cell adhesion molecule (CEACAM) family, which are frequently upregulated in epithelial cancers where they contribute to invasion, metastasis, immune evasion, and resistance to anoikis. CT109 is a novel antibody with dual specificity to both CEACAM5 and 6.

Objectives: In this study, we aimed to perform the preclinical characterization of CT109 and antibody- drug conjugate (ADCs) derivatives of CT109, focusing on CT109-SN-38.

Methods: CT109’s cognate epitope was characterized by scanning mutagenesis. CT109 specificity and internalization kinetics were assessed by immunoblot and flow cytometry, respectively. Cognate antigen expression prevalence in colorectal cancer and normal tissue arrays was determined by immunohistochemistry. CT109 conjugations were generated by the reaction of reduced CT109 cysteines with maleimide-functionalized payload linkers. In vitro cytotoxic activity of CT109 ADCs was characterized on antigen-positive and negative pancreatic ductal adenocarcinoma cell (PDAC) lines using a luminometric viability assay. In vivo efficacy of CT109-SN-38 was assessed on a PDAC tumor xenograft model at 10 and 25 mg/kg concentrations.

Results: CT109 was shown to bind a glycoepitope centered on N309. CT109 is internalized in the CEACAM5+/CEACAM6+ double-positive PDAC line, BxPC-3, with a t1/2 of 2.3 hours. CT109 ADCs elicit a dose and antigen-dependent cytotoxic effect, with CT109-SN-38 exhibiting an IC50 value of 21 nM in BxPC-3 cells. In a BxPC-3 tumor xenograft model, CT109-SN-38 reduced tumor growth and induced regression in 3/10 mice at a concentration 25 mg/kg.

Conclusion: These data suggest that further preclinical and clinical development of CT109-SN-38 is warranted.

« Previous Next »
Graphical Abstract

[1]
Kleist, S.V.; Chavanel, G.; Burtin, P. Identification of an antigen from normal human tissue that crossreacts with the carcinoembryonic antigen. Proc. Natl. Acad. Sci. USA, 1972, 69(9), 2492-2494.
[http://dx.doi.org/10.1073/pnas.69.9.2492] [PMID: 4115954]
[2]
Moore, T.L.; Kupchik, H.Z.; Marcon, N.; Zamcheck, N. Carcinoembryonic antigen assay in cancer of the colon and pancreas and other digestive tract disorders. Am. J. Dig. Dis., 1971, 16(1), 1-7.
[http://dx.doi.org/10.1007/BF02233781] [PMID: 5539559]
[3]
Coligan, J.E.; Lautenschleger, J.T.; Egan, M.L.; Todd, C.W. Isolation and characterization for carcinoembryonic antigen. Immunochemistry, 1972, 9(4), 377-386.
[http://dx.doi.org/10.1016/0019-2791(72)90308-4] [PMID: 4624559]
[4]
Gold, P.; Freedman, S.O. Specific carcinoembryonic antigens of the human digestive system. J. Exp. Med., 1965, 122(3), 467-481.
[http://dx.doi.org/10.1084/jem.122.3.467] [PMID: 4953873]
[5]
Blumenthal, R.D.; Leon, E.; Hansen, H.J.; Goldenberg, D.M. Expression patterns of CEACAM5 and CEACAM6 in primary and metastatic cancers. BMC Cancer, 2007, 7(1), 2.
[http://dx.doi.org/10.1186/1471-2407-7-2] [PMID: 17201906]
[6]
Zhang, X.; Han, X.; Zuo, P.; Zhang, X.; Xu, H. CEACAM5 stimulates the progression of non-small-cell lung cancer by promoting cell proliferation and migration. J. Int. Med. Res., 2020, 48(9)
[http://dx.doi.org/10.1177/0300060520959478] [PMID: 32993395]
[7]
Kuespert, K.; Pils, S.; Hauck, C.R. CEACAMs: their role in physiology and pathophysiology. Curr. Opin. Cell Biol., 2006, 18(5), 565-571.
[http://dx.doi.org/10.1016/j.ceb.2006.08.008] [PMID: 16919437]
[8]
Isacke, C.M.; Horton, M.A. CEACAM family; In: Adhes. Mol. FactsBook, 2000, pp. 103-107.
[http://dx.doi.org/10.1016/B978-012356505-1/50031-9]
[9]
Beauchemin, N.; Arabzadeh, A. Carcinoembryonic antigen-related cell adhesion molecules (CEACAMs) in cancer progression and metastasis. Cancer Metastasis Rev., 2013, 32(3-4), 643-671.
[http://dx.doi.org/10.1007/s10555-013-9444-6] [PMID: 23903773]
[10]
Pavlopoulou, A.; Scorilas, A. A comprehensive phylogenetic and structural analysis of the carcinoembryonic antigen (CEA) gene family. Genome Biol. Evol., 2014, 6(6), 1314-1326.
[http://dx.doi.org/10.1093/gbe/evu103] [PMID: 24858421]
[11]
Rizeq, B.; Zakaria, Z.; Ouhtit, A. Towards understanding the mechanisms of actions of carcinoembryonic antigen‐related cell adhesion molecule 6 in cancer progression. Cancer Sci., 2018, 109(1), 33-42.
[http://dx.doi.org/10.1111/cas.13437] [PMID: 29110374]
[12]
Zhu, R.; Ge, J.; Ma, J.; Zheng, J. Carcinoembryonic antigen related cell adhesion molecule 6 promotes the proliferation and migration of renal cancer cells through the ERK/AKT signaling pathway. Transl. Androl. Urol., 2019, 8(5), 457-466.
[http://dx.doi.org/10.21037/tau.2019.09.02] [PMID: 31807423]
[13]
Kim, E.Y.; Cha, Y.J.; Jeong, S.; Chang, Y.S. Overexpression of CEACAM6 activates Src-FAK signaling and inhibits anoikis, through homophilic interactions in lung adenocarcinomas. Transl. Oncol., 2022, 20, 101402.
[http://dx.doi.org/10.1016/j.tranon.2022.101402] [PMID: 35358791]
[14]
Duxbury, M.S.; Ito, H.; Benoit, E.; Waseem, T.; Ashley, S.W.; Whang, E.E. A novel role for carcinoembryonic antigen-related cell adhesion molecule 6 as a determinant of gemcitabine chemoresistance in pancreatic adenocarcinoma cells. Cancer Res., 2004, 64(11), 3987-3993.
[http://dx.doi.org/10.1158/0008-5472.CAN-04-0424] [PMID: 15173012]
[15]
Brümmer, J.; Ebrahimnejad, A.; Flayeh, R.; Schumacher, U.; Löning, T.; Bamberger, A.M.; Wagener, C. cis Interaction of the cell adhesion molecule CEACAM1 with integrin β(3). Am. J. Pathol., 2001, 159(2), 537-546.
[http://dx.doi.org/10.1016/S0002-9440(10)61725-7] [PMID: 11485912]
[16]
Camacho-Leal, P.; Zhai, A.B.; Stanners, C.P. A co-clustering model involving α5β1 integrin for the biological effects of GPI-anchored human carcinoembryonic antigen (CEA). J. Cell. Physiol., 2007, 211(3), 791-802.
[http://dx.doi.org/10.1002/jcp.20989] [PMID: 17286276]
[17]
Bonsor, D.A.; Günther, S.; Beadenkopf, R.; Beckett, D.; Sundberg, E.J. Diverse oligomeric states of CEACAM IgV domains. Proc. Natl. Acad. Sci. USA, 2015, 112(44), 13561-13566.
[http://dx.doi.org/10.1073/pnas.1509511112] [PMID: 26483485]
[18]
Pinkert, J.; Boehm, H.H.; Trautwein, M.; Doecke, W.D.; Wessel, F.; Ge, Y.; Gutierrez, E.M.; Carretero, R.; Freiberg, C.; Gritzan, U.; Luetke-Eversloh, M.; Golfier, S.; Von Ahsen, O.; Volpin, V.; Sorrentino, A.; Rathinasamy, A.; Xydia, M.; Lohmayer, R.; Sax, J.; Nur-Menevse, A.; Hussein, A.; Stamova, S.; Beckmann, G.; Glueck, J.M.; Schoenfeld, D.; Weiske, J.; Zopf, D.; Offringa, R.; Kreft, B.; Beckhove, P.; Willuda, J. T cell-mediated elimination of cancer cells by blocking CEACAM6–CEACAM1 interaction. OncoImmunology, 2022, 11(1), 2008110.
[http://dx.doi.org/10.1080/2162402X.2021.2008110] [PMID: 35141051]
[19]
Fantini, M.; David, J.M.; Annunziata, C.M.; Morelli, M.P.; Arlen, P.M.; Tsang, K.Y. The monoclonal antibody neo-201 enhances natural killer cell cytotoxicity against tumor cells through blockade of the inhibitory CEACAM5/CEACAM1 immune checkpoint pathway. Cancer Biother. Radiopharm., 2020, 35(3), 190-198.
[http://dx.doi.org/10.1089/cbr.2019.3141] [PMID: 31928422]
[20]
Kim, W.M.; Huang, Y.H.; Gandhi, A.; Blumberg, R.S. CEACAM1 structure and function in immunity and its therapeutic implications. Semin. Immunol., 2019, 42, 101296.
[http://dx.doi.org/10.1016/j.smim.2019.101296] [PMID: 31604530]
[21]
Kammerer, R.; Hahn, S.; Singer, B.B.; Jian, S. Luo; 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.
[http://dx.doi.org/10.1002/(SICI)1521-4141(199811)28:11<3664:AID-IMMU3664>3.0.CO;2-D] [PMID: 9842909]
[22]
Chen, Z.; Chen, L.; Qiao, S.-W.; Nagaishi, T.; Blumberg, R. S. Carcinoembryonic antigen-related cell adhesion molecule 1 inhibits proximal TCR signaling by targeting ZAP-70 J. Immunol. Baltim. Md 1950, 1950, 180(9), 6085-6093.
[http://dx.doi.org/10.4049/jimmunol.180.9.6085]
[23]
Ru, G.Q.; Han, Y.; Wang, W.; Chen, Y.; Wang, H.J.; Xu, W.J.; Ma, J.; Ye, M.; Chen, X.; He, X.L. Győrffy, B.; Zhao, Z.S.; Huang, D. CEACAM6 is a prognostic biomarker and potential therapeutic target for gastric carcinoma. Oncotarget, 2017, 8(48), 83673-83683.
[http://dx.doi.org/10.18632/oncotarget.19415] [PMID: 29137373]
[24]
Zhou, J.; Fan, X.; Chen, N.; Zhou, F.; Dong, J.; Nie, Y.; Fan, D. Identification of CEACAM5 as a biomarker for prewarning and prognosis in gastric cancer. J. Histochem. Cytochem., 2015, 63(12), 922-930.
[http://dx.doi.org/10.1369/0022155415609098] [PMID: 26374829]
[25]
Jantscheff, P.; Terracciano, L.; Lowy, A.; Glatz-Krieger, K.; Grunert, F.; Micheel, B.; Brümmer, J.; Laffer, U.; Metzger, U.; Herrmann, R.; Rochlitz, C. Expression of CEACAM6 in resectable colorectal cancer: a factor of independent prognostic significance. J. Clin. Oncol., 2003, 21(19), 3638-3646.
[http://dx.doi.org/10.1200/JCO.2003.55.135] [PMID: 14512395]
[26]
Vardakis, N.; Messaritakis, I.; Papadaki, C.; Agoglossakis, G.; Sfakianaki, M.; Saridaki, Z.; Apostolaki, S.; Koutroubakis, I.; Perraki, M.; Hatzidaki, D.; Mavroudis, D.; Georgoulias, V.; Souglakos, J. Prognostic significance of the detection of peripheral blood CEACAM5mRNA-positive cells by real-time polymerase chain reaction in operable colorectal cancer. Clin. Cancer Res., 2011, 17(1), 165-173.
[http://dx.doi.org/10.1158/1078-0432.CCR-10-0565] [PMID: 21071514]
[27]
Duxbury, M.S.; Matros, E.; Clancy, T.; Bailey, G.; Doff, M.; Zinner, M.J.; Ashley, S.W.; Maitra, A.; Redston, M.; Whang, E.E. CEACAM6 is a novel biomarker in pancreatic adenocarcinoma and PanIN lesions. Ann. Surg., 2005, 241(3), 491-496.
[http://dx.doi.org/10.1097/01.sla.0000154455.86404.e9] [PMID: 15729073]
[28]
Lu, Y.; Li, D.; Liu, G.; Xiao, E.; Mu, S.; Pan, Y.; Qin, F.; Zhai, Y.; Duan, S.; Li, D.; Yan, G. Identification of critical pathways and potential key genes in poorly differentiated pancreatic adenocarcinoma. OncoTargets Ther., 2021, 14, 711-723.
[http://dx.doi.org/10.2147/OTT.S279287] [PMID: 33536763]
[29]
Tsang, J.Y.S.; Kwok, Y.K.; Chan, K.W.; Ni, Y.B.; Chow, W.N.V.; Lau, K.F.; Shao, M.M.; Chan, S.K.; Tan, P.H.; Tse, G.M. Expression and clinical significance of carcinoembryonic antigen-related cell adhesion molecule 6 in breast cancers. Breast Cancer Res. Treat., 2013, 142(2), 311-322.
[http://dx.doi.org/10.1007/s10549-013-2756-y] [PMID: 24186057]
[30]
Ring, B.Z.; Seitz, R.S.; Beck, R.; Shasteen, W.J.; Tarr, S.M.; Cheang, M.C.U.; Yoder, B.J.; Budd, G.T.; Nielsen, T.O.; Hicks, D.G.; Estopinal, N.C.; Ross, D.T. Novel prognostic immunohistochemical biomarker panel for estrogen receptor-positive breast cancer. J. Clin. Oncol., 2006, 24(19), 3039-3047.
[http://dx.doi.org/10.1200/JCO.2006.05.6564] [PMID: 16809728]
[31]
Kobayashi, M.; Miki, Y.; Ebina, M.; Abe, K.; Mori, K.; Narumi, S.; Suzuki, T.; Sato, I.; Maemondo, M.; Endo, C.; Inoue, A.; Kumamoto, H.; Kondo, T.; Yamada-Okabe, H.; Nukiwa, T.; Sasano, H. Carcinoembryonic antigen-related cell adhesion molecules as surrogate markers for EGFR inhibitor sensitivity in human lung adenocarcinoma. Br. J. Cancer, 2012, 107(10), 1745-1753.
[http://dx.doi.org/10.1038/bjc.2012.422] [PMID: 23099808]
[32]
Benlloch, S.; Galbis-Caravajal, J.M.; Alenda, C.; Peiró, F.M.; Sanchez-Ronco, M.; Rodríguez-Paniagua, J.M.; Baschwitz, B.; Rojas, E.; Massutí, B. Expression of molecular markers in mediastinal nodes from resected stage I non-small-cell lung cancer (NSCLC): prognostic impact and potential role as markers of occult micrometastases. Ann. Oncol., 2009, 20(1), 91-97.
[http://dx.doi.org/10.1093/annonc/mdn538] [PMID: 18664559]
[33]
DeLucia, D.C.; Cardillo, T.M.; Ang, L.; Labrecque, M.P.; Zhang, A.; Hopkins, J.E.; De Sarkar, N.; Coleman, I.; da Costa, R.M.G.; Corey, E.; True, L.D.; Haffner, M.C.; Schweizer, M.T.; Morrissey, C.; Nelson, P.S.; Lee, J.K. Regulation of CEACAM5 and therapeutic efficacy of an anti-CEACAM5–SN38 antibody–drug conjugate in neuroendocrine prostate cancer. Clin. Cancer Res., 2021, 27(3), 759-774.
[http://dx.doi.org/10.1158/1078-0432.CCR-20-3396] [PMID: 33199493]
[34]
Ameur, N.; Lacroix, L.; Roucan, S.; Roux, V.; Broutin, S.; Talbot, M.; Dupuy, C.; Caillou, B.; Schlumberger, M.; Bidart, J.M. Aggressive inherited and sporadic medullary thyroid carcinomas display similar oncogenic pathways. Endocr. Relat. Cancer, 2009, 16(4), 1261-1272.
[http://dx.doi.org/10.1677/ERC-08-0289] [PMID: 19675075]
[35]
Krueger, P.; Nitz, C.; Foster, R.; MacDonald, C.; Gelber, O.; Lalehzadeh, G.; Goodson, R.; Winter, J.; Gelber, C. A new small cell lung cancer (SCLC)-specific marker discovered through antigenic subtraction of neuroblastoma cells. Cancer Immunol. Immunother., 2003, 52(6), 367-377.
[http://dx.doi.org/10.1007/s00262-003-0376-9] [PMID: 12669243]
[36]
Hatakeyama, K.; Wakabayashi-Nakao, K.; Ohshima, K.; Sakura, N.; Yamaguchi, K.; Mochizuki, T. Novel protein isoforms of carcinoembryonic antigen are secreted from pancreatic, gastric and colorectal cancer cells. BMC Res. Notes, 2013, 6(1), 381.
[http://dx.doi.org/10.1186/1756-0500-6-381] [PMID: 24070190]
[37]
Eaton, J.S.; Miller, P.E.; Mannis, M.J.; Murphy, C.J. Ocular adverse events associated with antibody–drug conjugates in human clinical trials. J. Ocul. Pharmacol. Ther., 2015, 31(10), 589-604.
[http://dx.doi.org/10.1089/jop.2015.0064] [PMID: 26539624]
[38]
Bechmann, M.B.; Brydholm, A.V.; Codony, V.L.; Kim, J.; Villadsen, R. Heterogeneity of CEACAM5 in breast cancer. Oncotarget, 2020, 11(43), 3886-3899.
[http://dx.doi.org/10.18632/oncotarget.27778] [PMID: 33196697]
[39]
Han, S-U.; Kwak, T-H.; Her, K.H.; Cho, Y-H.; Choi, C.; Lee, H-J.; Hong, S.; Park, Y.S.; Kim, Y-S.; Kim, T-A.; Kim, S-J. CEACAM5 and CEACAM6 are major target genes for Smad3-mediated TGF-β signaling. Oncogene, 2008, 27(5), 675-683.
[http://dx.doi.org/10.1038/sj.onc.1210686] [PMID: 17653079]
[40]
Schmidt, M.M.; Thurber, G.M.; Wittrup, K.D. Kinetics of anti-carcinoembryonic antigen antibody internalization: effects of affinity, bivalency, and stability. Cancer Immunol. Immunother., 2008, 57(12), 1879-1890.
[http://dx.doi.org/10.1007/s00262-008-0518-1] [PMID: 18408925]
[41]
Oba, A.; Ho, F.; Bao, Q.R.; Al-Musawi, M.H.; Schulick, R.D.; Del Chiaro, M. Neoadjuvant treatment in pancreatic cancer. Front. Oncol., 2020, 10, 245.
[http://dx.doi.org/10.3389/fonc.2020.00245] [PMID: 32185128]
[42]
Huang, L.; Li, T.J.; Zhang, J.W.; Liu, S.; Fu, B.S.; Liu, W. Neoadjuvant chemotherapy followed by surgery versus surgery alone for colorectal cancer: meta-analysis of randomized controlled trials. Medicine (Baltimore), 2014, 93(28), e231.
[http://dx.doi.org/10.1097/MD.0000000000000231] [PMID: 25526442]
[43]
Goldenberg, D.M.; Sharkey, R.M. Antibody-drug conjugates targeting TROP-2 and incorporating SN-38: A case study of anti-TROP-2 sacituzumab govitecan. MAbs, 2019, 11(6), 987-995.
[http://dx.doi.org/10.1080/19420862.2019.1632115] [PMID: 31208270]
[44]
Hirose, K.; Kozu, C.; Yamashita, K.; Maruo, E.; Kitamura, M.; Hasegawa, J.; Omoda, K.; Murakami, T.; Maeda, Y. Correlation between plasma concentration ratios of SN-38 glucuronide and SN-38 and neutropenia induction in patients with colorectal cancer and wild-type UGT1A1 gene. Oncol. Lett., 2012, 3(3), 694-698.
[http://dx.doi.org/10.3892/ol.2011.533] [PMID: 22740978]
[45]
Yurkovetskiy, A.V.; Yin, M.; Bodyak, N.; Stevenson, C.A.; Thomas, J.D.; Hammond, C.E.; Qin, L.; Zhu, B.; Gumerov, D.R.; Ter-Ovanesyan, E.; Uttard, A.; Lowinger, T.B. A polymer-based antibody–vinca drug conjugate platform: characterization and preclinical efficacy. Cancer Res., 2015, 75(16), 3365-3372.
[http://dx.doi.org/10.1158/0008-5472.CAN-15-0129] [PMID: 26113086]
[46]
Schellenberger, V.; Wang, C.; Geething, N.C.; Spink, B.J.; Campbell, A.; To, W.; Scholle, M.D.; Yin, Y.; Yao, Y.; Bogin, O.; Cleland, J.L.; Silverman, J.; Stemmer, W.P.C. A recombinant polypeptide extends the in vivo half-life of peptides and proteins in a tunable manner. Nat. Biotechnol., 2009, 27(12), 1186-1190.
[http://dx.doi.org/10.1038/nbt.1588] [PMID: 19915550]
[47]
Zacharias, N.; Podust, V.N.; Kajihara, K.K.; Leipold, D.; Del Rosario, G.; Thayer, D.; Dong, E.; Paluch, M.; Fischer, D.; Zheng, K.; Lei, C.; He, J.; Ng, C.; Su, D.; Liu, L.; Masih, S.; Sawyer, W.; Tinianow, J.; Marik, J.; Yip, V.; Li, G.; Chuh, J.; Morisaki, J.H.; Park, S.; Zheng, B.; Hernandez-Barry, H.; Loyet, K.M.; Xu, M.; Kozak, K.R.; Phillips, G.L.; Shen, B.Q.; Wu, C.; Xu, K.; Yu, S.F.; Kamath, A.; Rowntree, R.K.; Reilly, D.; Pillow, T.; Polson, A.; Schellenberger, V.; Hazenbos, W.L.W.; Sadowsky, J. A homogeneous high-DAR antibody–drug conjugate platform combining THIOMAB antibodies and XTEN polypeptides. Chem. Sci., 2022, 13(11), 3147-3160.
[http://dx.doi.org/10.1039/D1SC05243H] [PMID: 35414872]
[48]
Junutula, J.R.; Bhakta, S.; Raab, H.; Ervin, K.E.; Eigenbrot, C.; Vandlen, R.; Scheller, R.H.; Lowman, H.B. Rapid identification of reactive cysteine residues for site-specific labeling of antibody-Fabs. J. Immunol. Methods, 2008, 332(1-2), 41-52.
[http://dx.doi.org/10.1016/j.jim.2007.12.011] [PMID: 18230399]
[49]
Chen, X.N.; Nguyen, M.; Jacobson, F.; Ouyang, J. Charge-based analysis of antibodies with engineered cysteines. MAbs, 2009, 1(6), 563-571.
[http://dx.doi.org/10.4161/mabs.1.6.10058] [PMID: 20068389]
[50]
Ackerman, S.E.; Pearson, C.I.; Gregorio, J.D.; Gonzalez, J.C.; Kenkel, J.A.; Hartmann, F.J.; Luo, A.; Ho, P.Y.; LeBlanc, H.; Blum, L.K.; Kimmey, S.C.; Luo, A.; Nguyen, M.L.; Paik, J.C.; Sheu, L.Y.; Ackerman, B.; Lee, A.; Li, H.; Melrose, J.; Laura, R.P.; Ramani, V.C.; Henning, K.A.; Jackson, D.Y.; Safina, B.S.; Yonehiro, G.; Devens, B.H.; Carmi, Y.; Chapin, S.J.; Bendall, S.C.; Kowanetz, M.; Dornan, D.; Engleman, E.G.; Alonso, M.N. Immune-stimulating antibody conjugates elicit robust myeloid activation and durable antitumor immunity. Nat. Can., 2020, 2(1), 18-33.
[http://dx.doi.org/10.1038/s43018-020-00136-x] [PMID: 35121890]
[51]
Fang, S.; Brems, B.M.; Olawode, E.O.; Miller, J.T.; Brooks, T.A.; Tumey, L.N. Design and characterization of immune-stimulating imidazo[4,5-c]quinoline antibody-drug conjugates. Mol. Pharm., 2022, 19(9), 3228-3241.
[http://dx.doi.org/10.1021/acs.molpharmaceut.2c00392] [PMID: 35904247]
[52]
Huehls, A.M.; Coupet, T.A.; Sentman, C.L. Bispecific T‐cell engagers for cancer immunotherapy. Immunol. Cell Biol., 2015, 93(3), 290-296.
[http://dx.doi.org/10.1038/icb.2014.93] [PMID: 25367186]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy