CAR-T Therapy for Solid Tumors: Development of New Strategies
Vol 4, Issue 2, 2020
VIEWS - 4020 (Abstract)
Abstract
The recent approval of two CAR-T therapies by US Food and Drug Administration (FDA) marks a very significant development in cell-based cancer immunotherapy. This milestone was demonstrated by the effectiveness of eradicating hematologic cancers using CD19-specific CARs. The success spurred development of immune cell therapies for other cancers, especially solid tumors. The generation of novel CAR constructs for these cancer types represents a major challenge in bringing the technology ‘from-bench-to-bedside‘.In this review, we outline some new technologies we have developed to equip CAR-T cells to enhance efficiency while decreasing toxicity of CAR-T therapies in solid tumors.
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- Huang, H., Jin, J., & Li, X. (2014). Re: Factors affecting recurrence and progression of high grade noninvasive bladder cancer treated by intravesical BCG. Pakistan Journal of Medical Sciences, 30(6). doi:10.12669/pjms.306.6408
- Colombo, N., Lorusso, D., & Scollo, P. (2017). Impact of Recurrence of Ovarian Cancer on Quality of Life and Outlook for the Future. International Journal of Gynecological Cancer, 27(6), 1134-1140. doi:10.1097/igc.0000000000001023
- Mayor, S. (2017). Risk of breast cancer recurrence remains for years after endocrine treatment ends, study finds. Bmj. doi:10.1136/bmj.j5167
- Hong, B., & Zu, Y. (2013). Detecting Circulating Tumor Cells: Current Challenges and New Trends. Theranostics, 3(6), 377-394. doi:10.7150/thno.5195
- Andree, K. C., Dalum, G. V., & Terstappen, L. W. (2015). Challenges in circulating tumor cell detection by the CellSearch system. Molecular Oncology, 10(3), 395-407. doi:10.1016/j.molonc.2015.12.002
- Al-Azri, M. H. (2016). Delay in Cancer Diagnosis: Causes and Possible Solutions. Oman Medical Journal, 31(5), 325-326. doi:10.5001/omj.2016.65
- Walter, F. M., Rubin, G., Bankhead, C., Morris, H. C., Hall, N., Mills, K., Emery, J. (2015). Symptoms and other factors associated with time to diagnosis and stage of lung cancer: A prospective cohort study. British Journal of Cancer, 112(S1). doi:10.1038/bjc.2015.30
- Zahreddine, H., & Borden, K. L. (2013). Mechanisms and insights into drug resistance in cancer. Frontiers in Pharmacology, 4. doi:10.3389/fphar.2013.00028
- Cornell, R. F., & Kassim, A. A. (2016). Evolving paradigms in the treatment of relapsed/refractory multiple myeloma: Increased options and increased complexity. Bone Marrow Transplantation, 51(4), 479-491. doi:10.1038/bmt.2015.307
- Schulze, A. B., & Schmidt, L. H. (2017). PD-1 targeted Immunotherapy as first-line therapy for advanced non-small-cell lung cancer patients. Journal of Thoracic Disease, 9(4). doi:10.21037/jtd.2017.03.118
- Tessema, F. A., & Darrow, J. J. (2017). A New Approach to Treat Childhood Leukemia: Novartis CAR-T Therapy. The Journal of Law, Medicine & Ethics, 45(4), 692-697. doi:10.1177/1073110517750609
- Jain, M. D., Bachmeier, C. A., Phuoc, V. H., & Chavez, J. C. (2018). Axicabtagene ciloleucel (KTE-C19), an anti-CD19 CAR T therapy for the treatment of relapsed/refractory aggressive B-cell non-Hodgkin’s lymphoma. Therapeutics and Clinical Risk Management, Volume 14, 1007-1017. doi:10.2147/tcrm.s145039
- Rappl, G., Riet, T., Awerkiew, S., Schmidt, A., Hombach, A. A., Pfister, H., & Abken, H. (2012). The CD3-Zeta Chimeric Antigen Receptor Overcomes TCR Hypo-Responsiveness of Human Terminal Late-Stage T Cells. PLoS ONE, 7(1). doi:10.1371/journal.pone.0030713
- Munisvaradass, R., Kumar, S., Govindasamy, C., Alnumair, K., & Mok, P. (2017). Human CD3 T-Cells with the Anti-ERBB2 Chimeric Antigen Receptor Exhibit Efficient Targeting and Induce Apoptosis in ERBB2 Overexpressing Breast Cancer Cells. International Journal of Molecular Sciences, 18(9), 1797. doi:10.3390/ijms18091797
- Yi, Z., Prinzing, B. L., Cao, F., Gottschalk, S., & Krenciute, G. (2018). Optimizing EphA2-CAR T Cells for the Adoptive Immunotherapy of Glioma. Molecular Therapy - Methods & Clinical Development, 9, 70-80. doi:10.1016/j.omtm.2018.01.009
- Gross, G., Waks, T., & Eshhar, Z. (1989). Expression of immunoglobulin-T-cell receptor chimeric molecules as functional receptors with antibody-type specificity. Proceedings of the National Academy of Sciences, 86(24), 10024-10028. doi:10.1073/pnas.86.24.10024
- Irving, B. A., & Weiss, A. (1991). The cytoplasmic domain of the T cell receptor chain is sufficient to couple to receptor-associated signal transduction pathways. Cell, 64(5), 891-901. doi:10.1016/0092-8674(91)90314-o
- Brentjens, R. J., Nikhamin, Y., Matsushita, M., & Sadelain, M. (2005). In Vitro and In Vivo Characterization of “Second-Generation” Co-Stimulatory Chimeric Antigen Receptors (CARs) Targeting the CD19 Antigen Present on B Cell Malignancies. Molecular Therapy, 11. doi:10.1016/j.ymthe.2005.07.336
- Tang, X., Sun, Y., Zhang, A., Hu, G., Cao, W., Wang, D., Chen, H. (2016). Third-generation CD28/4-1BB chimeric antigen receptor T cells for chemotherapy relapsed or refractory acute lymphoblastic leukaemia: A non-randomised, open-label phase I trial protocol. BMJ Open, 6(12). doi:10.1136/bmjopen-2016-013904
- Hombach, A. A., Heiders, J., Foppe, M., Chmielewski, M. & Abken, H. (2012). OX40 costimulation by a chimeric antigen receptor abrogates CD28 and IL-2 induced IL-10 secretion by redirected CD4(+) T cells. Oncoimmunology, 1 (4): 458-466.
- Guedan, S., Posey, A.D. Jr., Shaw, C., Wing, A., June, C.H. (2018). Enhancing CAR T cell persistence through ICOS and 4-1BB costimulation. JCI Insight, 3 (1): pii.96976. doi: 10.1172/jci.insight.96976
- Song, D.G., Ye, Q., Poussin, M., Harms, G.M., Figini, M., Powell, D.J. Jr. (2012). CD27 costimulation augments the survival and antitumor activity of redirected human T cells in vivo. Blood, 119:696–706. doi: 10.1182/blood-2011-03-344275
- Chmielewski, M., & Abken, H. (2017). CAR T Cells Releasing IL-18 Convert to T-Bet high FoxO1 low Effectors that Exhibit Augmented Activity against Advanced Solid Tumors. Cell Reports, 21(11), 3205-3219. doi:10.1016/j.celrep.2017.11.063
- Zhang, L-N., Song, Y. and Liu, D. (2018). CD19 CAR-T cell therapy for relapsed/refractory acute lymphoblastic leukemia: factors affecting toxicities and long term efficacies. Journal of Hematology & Oncology, 11: 41. doi: 10.1186/s13045-018-0593-5
- Ma, J.S., Kim, J.Y., Kazane, S.A., Choi, S.H., Cao, Y. (2016). Versatile strategy for controlling the specificity and activity of engineered T cells. Proc Natl Acad Sci USA, 113 (4): E450-8. doi: 10.1073/pnas.1524193113
- Mirzaei, H. R., Rodriguez, A., Shepphird, J., Brown, C. E., & Badie, B. (2017). Chimeric Antigen Receptors T Cell Therapy in Solid Tumor: Challenges and Clinical Applications. Frontiers in Immunology, 8. doi:10.3389/fimmu.2017.01850
- D’Aloia, M.M., Zizzari, I.G., Sacchetti, B., Pierelli, L. & Alimandi, M. (2018). CAR-T cells: the long and winding road to solid tumors. Cell Death Dis, 9 (3): 282. doi: 10.1038/s41419-018-0278-6
- Hu, M., Li, K., Maskey, N., Xu, Z., Yu, F., Peng, C., Yang, G. (2015). Overexpression of the chemokine receptor CXCR3 and its correlation with favorable prognosis in gastric cancer. Human Pathology, 46(12), 1872-1880. doi:10.1016/j.humpath.2015.08.004
- Postow, M. (2016). Faculty of 1000 evaluation for Non-redundant requirement for CXCR3 signalling during tumoricidal T-cell trafficking across tumour vascular checkpoints. F1000 - Post-publication Peer Review of the Biomedical Literature. doi:10.3410/f.725587207.793524109
- Harlin, H., Meng, Y., Peterson, A. C., Zha, Y., Tretiakova, M., Slingluff, C., Gajewski, T. F. (2009). Chemokine Expression in Melanoma Metastases Associated with CD8 T-Cell Recruitment. Cancer Research, 69(7), 3077-3085. doi:10.1158/0008-5472.can-08-2281
- Craddock, J. A., Lu, A., Bear, A., Pule, M., Brenner, M. K., Rooney, C. M., & Foster, A. E. (2010). Enhanced Tumor Trafficking of GD2 Chimeric Antigen Receptor T Cells by Expression of the Chemokine Receptor CCR2b. Journal of Immunotherapy, 33(8), 780-788. doi:10.1097/cji.0b013e3181ee6675
- Peng, W., Ye, Y., Rabinovich, B. A., Liu, C., Lou, Y., Zhang, M., Hwu, P. (2010). Transduction of Tumor-Specific T Cells with CXCR2 Chemokine Receptor Improves Migration to Tumor and Antitumor Immune Responses. Clinical Cancer Research, 16(22), 5458-5468. doi:10.1158/1078-0432.ccr-10-0712
- Stasi, A. D., Angelis, B. D., Rooney, C. M., Zhang, L., Mahendravada, A., Foster, A. E., Savoldo, B. (2009). T lymphocytes coexpressing CCR4 and a chimeric antigen receptor targeting CD30 have improved homing and antitumor activity in a Hodgkin tumor model. Blood, 113(25), 6392-6402. doi:10.1182/blood-2009-03-209650
- Newick, K., Obrien, S., Sun, J., Kapoor, V., Maceyko, S., Lo, A., . . . Albelda, S. M. (2016). Augmentation of CAR T-cell Trafficking and Antitumor Efficacy by Blocking Protein Kinase A Localization. Cancer Immunology Research, 4(6), 541-551. doi:10.1158/2326-6066.cir-15-0263
- ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). Identifier NCT03500991. HER2-specific CAR T Cell Locoregional Immunotherapy for HER2-positive Recurrent/Refractory Pediatric CNS Tumors. (n.d.). Cited 2018 June 22. Retrieved from https://clinicaltrials.gov/ct2/show/NCT03500991
- ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). Identifier NCT02850536. CAR-T Hepatic Artery Infusions or Pancreatic Venous Infusions for CEA-Expressing Liver Metastases or Pancreas Cancer. (n.d.). Cited 2018 June 22. Retrieved from https://clinicaltrials.gov/ct2/show/NCT02850536
- ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). Identifier NCT01818323. Phase I Trial: T4 Immunotherapy of Head and Neck Cancer. (n.d.). Cited 2018 June 22. Retrieved from https://clinicaltrials.gov/ct2/show/NCT01818323
- Ajina, A., & Maher, J. (2017). Prospects for combined use of oncolytic viruses and CAR T-cells. Journal for ImmunoTherapy of Cancer, 5(1). doi:10.1186/s40425-017-0294-6
- Moon, E. K., Wang, L. S., Bekdache, K., Lynn, R. C., Lo, A., Thorne, S. H., & Albelda, S. M. (2018). Intra-tumoral delivery of CXCL11 via a vaccinia virus, but not by modified T cells, enhances the efficacy of adoptive T cell therapy and vaccines. OncoImmunology, 7(3). doi:10.1080/2162402x.2017.1395997
- Li, J., Omalley, M., Urban, J., Sampath, P., Guo, Z. S., Kalinski, P., Bartlett, D. L. (2011). Chemokine Expression From Oncolytic Vaccinia Virus Enhances Vaccine Therapies of Cancer. Molecular Therapy, 19(4), 650-657. doi:10.1038/mt.2010.312
- Li, J., Omalley, M., Sampath, P., Kalinski, P., Bartlett, D. L., & Thorne, S. H. (2012). Expression of CCL19 from Oncolytic Vaccinia Enhances Immunotherapeutic Potential while Maintaining Oncolytic Activity. Neoplasia, 14(12). doi:10.1593/neo.121272
- Afanasiev, O. K., Nagase, K., Simonson, W., Vandeven, N., Blom, A., Koelle, D. M., Nghiem, P. (2013). Vascular E-Selectin Expression Correlates with CD8 Lymphocyte Infiltration and Improved Outcome in Merkel Cell Carcinoma. Journal of Investigative Dermatology, 133(8), 2065-2073. doi:10.1038/jid.2013.36
- Ley, K., & Kansas, G. S. (2004). Selectins in T-cell recruitment to non-lymphoid tissues and sites of inflammation. Nature Reviews Immunology, 4(5), 325-336. doi:10.1038/nri1351
- Chae, Y. K., Choi, W. M., Bae, W. H., Anker, J., Davis, A. A., Agte, S., Giles, F. J. (2018). Overexpression of adhesion molecules and barrier molecules is associated with differential infiltration of immune cells in non-small cell lung cancer. Scientific Reports, 8(1). doi:10.1038/s41598-018-19454-3
- Anderson, K. G., Stromnes, I. M., & Greenberg, P. D. (2017). Obstacles Posed by the Tumor Microenvironment to T cell Activity: A Case for Synergistic Therapies. Cancer Cell, 31(3), 311-325. doi:10.1016/j.ccell.2017.02.008
- Caruana, I., Savoldo, B., Hoyos, V., Weber, G., Liu, H., Kim, E. S., Dotti, G. (2015). Heparanase promotes tumor infiltration and antitumor activity of CAR-redirected T lymphocytes. Nature Medicine, 21(5), 524-529. doi:10.1038/nm.3833
- Sengupta, S., Mohan, N., Chiocca, E. A., Sampath, P., & Viapiano, M. (2016). Novel Car-T Cells Targeting The Extracellular Matrix Of Glioblastoma Induce Strong Anti-Tumor Immune Response. Neuro-Oncology, 18. Vi86-Vi87. doi:10.1093/neuonc/now212.362
- Huang, K., Hsiao, Y., Wu, T., Huang, A., Ai, L., & Kuan, C. (2018). Targeting of vegfr2-expressing cells by chimeric antigen receptor (car) t cells for solid tumour therapy. Immunotherapy and Cancer Vaccines. doi:10.1136/esmoopen-2018-eacr25.937
- Mckee, T. D., Grandi, P., Mok, W., Alexandrakis, G., Insin, N., Zimmer, J. P., Jain, R. K. (2006). Degradation of Fibrillar Collagen in a Human Melanoma Xenograft Improves the Efficacy of an Oncolytic Herpes Simplex Virus Vector. Cancer Research, 66(5), 2509-2513. doi:10.1158/0008-5472.can-05-2242
- Guedan, S., Rojas, J. J., Gros, A., Mercade, E., Cascallo, M., & Alemany, R. (2010). Hyaluronidase Expression by an Oncolytic Adenovirus Enhances Its Intratumoral Spread and Suppresses Tumor Growth. Molecular Therapy, 18(7), 1275-1283. doi:10.1038/mt.2010.79
- Schäfer, S., Weibel, S., Donat, U., Zhang, Q., Aguilar, R. J., Chen, N. G., & Szalay, A. A. (2012). Vaccinia virus-mediated intra-tumoral expression of matrix metalloproteinase 9 enhances oncolysis of PC-3 xenograft tumors. BMC Cancer, 12(1). doi:10.1186/1471-2407-12-366
- Hou, W., Chen, H., Rojas, J., Sampath, P., & Thorne, S. H. (2014). Oncolytic vaccinia virus demonstrates antiangiogenic effects mediated by targeting of VEGF. International Journal of Cancer, 135(5), 1238-1246. doi:10.1002/ijc.28747
- Adelfinger, M., Bessler, S., Frentzen, A., Cecil, A., Langbein-Laugwitz, J., Gentschev, I., & Szalay, A. (2015). Preclinical Testing Oncolytic Vaccinia Virus Strain GLV-5b451 Expressing an Anti-VEGF Single-Chain Antibody for Canine Cancer Therapy. Viruses, 7(7), 4075-4092. doi:10.3390/v7072811
- Currier, M. A., Eshun, F. K., Sholl, A., Chernoguz, A., Crawford, K., Divanovic, S., Cripe, T. P. (2013). VEGF Blockade Enables Oncolytic Cancer Virotherapy in Part by Modulating Intratumoral Myeloid Cells. Molecular Therapy, 21(5), 1014-1023. doi:10.1038/mt.2013.39
- Hayes, A. J., Huang, W-Q., Yu, J., Li, L-Y. (2000). Expression and function of angiopoietin-1 in breast cancer. Br J Cancer, 83 (9): 1154-1160. doi: 10.1054/bjoc.2000.1437
- Kim, I., Moon, S., Park, S. K., Chae, S. W., & Koh, G. Y. (2001). Angiopoietin-1 Reduces VEGF-Stimulated Leukocyte Adhesion to Endothelial Cells by Reducing ICAM-1, VCAM-1, and E-Selectin Expression. Circulation Research, 89(6), 477-479. doi:10.1161/hh1801.097034
- Whiteside, T. L. (2008). The tumor microenvironment and its role in promoting tumor growth. Oncogene, 27(45), 5904-5912. doi:10.1038/onc.2008.271
- Baum, J., & Duffy, H. S. (2011). Fibroblasts and Myofibroblasts: What Are We Talking About? Journal of Cardiovascular Pharmacology, 57(4), 376-379. doi:10.1097/fjc.0b013e3182116e39
- Shiga, K., Hara, M., Nagasaki, T., Sato, T., Takahashi, H., & Takeyama, H. (2015). Cancer-Associated Fibroblasts: Their Characteristics and Their Roles in Tumor Growth. Cancers, 7(4), 2443-2458. doi:10.3390/cancers7040902
- Tao, L., Huang, G., Song, H., Chen, Y., & Chen, L. (2017). Cancer associated fibroblasts: An essential role in the tumor microenvironment. Oncology Letters, 14(3), 2611-2620. doi:10.3892/ol.2017.6497
- Räsänen, K., & Vaheri, A. (2010). Activation of fibroblasts in cancer stroma. Experimental Cell Research, 316(17), 2713-2722. doi:10.1016/j.yexcr.2010.04.032
- Franses, J. W., Baker, A. B., Chitalia, V. C., & Edelman, E. R. (2011). Stromal Endothelial Cells Directly Influence Cancer Progression. Science Translational Medicine, 3(66). doi:10.1126/scitranslmed.3001542
- Maishi, N., & Hida, K. (2017). Tumor endothelial cells accelerate tumor metastasis. Cancer Science, 108(10), 1921-1926. doi:10.1111/cas.13336
- Ribeiro, A. and Okamoto, O. K. (2015). Combined effects of pericytes in the tumor microenvironment. Stem Cells Int, v2015. doi: 10.1155/2015/868475
- Pircher, M., Schuberth, P., Gulati, P., Sulser, S., Weder, W., Curioni, A., Petrausch, U. (2015). FAP-specific re-directed T cells first in-man study in malignant pleural mesothelioma: Experience of the first patient treated. Journal for ImmunoTherapy of Cancer, 3. doi:10.1186/2051-1426-3-s2-p120
- Facciabene, A., Motz, G. T., & Coukos, G. (2012). T-Regulatory Cells: Key Players in Tumor Immune Escape and Angiogenesis. Cancer Research, 72(9), 2162-2171. doi:10.1158/0008-5472.can-11-3687
- Sarvaria, A., Madrigal, J. A., & Saudemont, A. (2017). B cell regulation in cancer and anti-tumor immunity. Cellular & Molecular Immunology, 14(8), 662-674. doi:10.1038/cmi.2017.35
- Hasmim, M., Messai, Y., Ziani, L., Thiery, J., Bouhris, J., Noman, M. Z., & Chouaib, S. (2015). Critical Role of Tumor Microenvironment in Shaping NK Cell Functions: Implication of Hypoxic Stress. Frontiers in Immunology, 6. doi:10.3389/fimmu.2015.00482
- Mcdonnell, A. M., Lesterhuis, W. J., Khong, A., Nowak, A. K., Lake, R. A., Currie, A. J., & Robinson, B. W. (2014). Tumor-infiltrating dendritic cells exhibit defective cross-presentation of tumor antigens, but is reversed by chemotherapy. European Journal of Immunology, 45(1), 49-59. doi:10.1002/eji.201444722
- Jackute, J., Zemaitis, M., Pranys, D., Sitkauskiene, B., Miliauskas, S., Vaitkiene, S., & Sakalauskas, R. (2018). Distribution of M1 and M2 macrophages in tumor islets and stroma in relation to prognosis of non-small cell lung cancer. BMC Immunology, 19(1). doi:10.1186/s12865-018-0241-4
- Medrek, C., Pontén, F., Jirström, K., & Leandersson, K. (2012). The presence of tumor associated macrophages in tumor stroma as a prognostic marker for breast cancer patients. BMC Cancer, 12(1). doi:10.1186/1471-2407-12-306
- Umansky, V., & Sevko, A. (2012). Tumor Microenvironment and Myeloid-Derived Suppressor Cells. Cancer Microenvironment, 6(2), 169-177. doi:10.1007/s12307-012-0126-7
- Gregory, A. D., & Houghton, A. M. (2011). Tumor-Associated Neutrophils: New Targets for Cancer Therapy. Cancer Research, 71(7), 2411-2416. doi:10.1158/0008-5472.can-10-2583
- Vona-Davis, L. and Gibson, L. (2013). Adipocytes as a critical component of the tumor microenvironment. Leuk Res, 37 (5): 483-848. doi: 10.1016/j.leukres.2013.01.007
- Bussard, K. M., Mutkus, L., Stumpf, K., Marini, F. C. (2016). Tumor-associated stromal cells as key contributors to the tumor microenvironment. Breast Cancer Res, 18 (84). doi: 10.1186/s13058-016-0740-2
- Li, H., Fan, X. and Houghton, J. (2007). Tumor microenvironment: the role of the tumor stroma in cancer. J Cell Biochem, 101: 805-815. doi: 10.1002/jcb.21159
- Westendorf, A., Skibbe, K., Adamczyk, A., Buer, J., Geffers, R., Hansen, W., Jendrossek, V. (2017). Hypoxia Enhances Immunosuppression by Inhibiting CD4 Effector T Cell Function and Promoting Treg Activity. Cellular Physiology and Biochemistry, 41(4), 1271-1284. doi:10.1159/000464429
- Semenza, G. L. (2006). Regulation of physiological responses to continuous and intermittent hypoxia by hypoxia-inducible factor 1. Experimental Physiology, 91(5), 803-806. doi:10.1113/expphysiol.2006.033498
- Silly, R. V., Derouazi, M., Dietrich, P. Y., & Walker, P. R. (2015). Hypoxia promotes IL-10 secretion by reactivated CTLs while limiting their expansion. Annals of Oncology, 26(Suppl 8), Viii14-Viii14. doi:10.1093/annonc/mdv514.35
- Juillerat, A., Marechal, A., Filhol, J. M., Valogne, Y., Valton, J., Duclert, A., Poirot, L. (2017). An oxygen sensitive self-decision making engineered CAR T-cell. Scientific Reports, 7(1). doi:10.1038/srep39833
- Lucas, A. T., Price, L. S., Schorzman, A. N., Storrie, M., Piscitelli, J. A., Razo, J., & Zamboni, W. C. (2018). Factors Affecting the Pharmacology of Antibody–Drug Conjugates. Antibodies, 7(10). doi:10.3390/antib7010010
- Park, S., Shevlin, E., Vedvyas, Y., Zaman, M., Park, S., Min, I. M., & Jin, M. M. (2017). Micromolar affinity CAR T cells to ICAM-1 achieves rapid tumor elimination while avoiding systemic toxicity. Cancer Research, 77, 3750-3750. doi:10.1158/1538-7445.am2017-3750
- Liu, X., Jiang, S., Fang, C., Yang, S., Olalere, D., Pequignot, E. C., Zhao, Y. (2015). Affinity-Tuned ErbB2 or EGFR Chimeric Antigen Receptor T Cells Exhibit an Increased Therapeutic Index against Tumors in Mice. Cancer Research, 75(17), 3596-3607. doi:10.1158/0008-5472.can-15-0159
- Li, D., Wang, L., Maziuk, B. F., Yao, X., Wolozin, B., & Cho, Y. K. (2018). Directed evolution of a picomolar-affinity, high-specificity antibody targeting phosphorylated tau. Journal of Biological Chemistry, 293(31), 12081-12094. doi:10.1074/jbc.ra118.003557
- Chiu, M. L., & Gilliland, G. L. (2016). Engineering antibody therapeutics. Current Opinion in Structural Biology, 38, 163-173. doi:10.1016/j.sbi.2016.07.012
- Li, K., Zettlitz, K. A., Lipianskaya, J., Zhou, Y., Marks, J. D., Mallick, P., Wu, A. M. (2015). A fully human scFv phage display library for rapid antibody fragment reformatting. Protein Engineering Design and Selection, 28(10), 307-316. doi:10.1093/protein/gzv024
- Davila, M. and Brentjens, R. (2016). CD19-targeted CAR T cells as novel cancer immunotherapy for relapsed or refractory B-cell acute lymphoblastic leukemia. Clin Adv Hematol Oncol, 14 (10): 802-808.
- Tasian, S. K., & Gardner, R. A. (2015). CD19-redirected chimeric antigen receptor-modified T cells: A promising immunotherapy for children and adults with B-cell acute lymphoblastic leukemia (ALL). Therapeutic Advances in Hematology, 6(5), 228-241. doi:10.1177/2040620715588916
- Watanabe, N., Bajgain, P., Sukumaran, S., Ansari, S., Heslop, H. E., Rooney, C. M., Vera, J. F. (2016). Fine-tuning the CAR spacer improves T-cell potency. OncoImmunology, 5(12). doi:10.1080/2162402x.2016.1253656
- Lu, Y., & Robbins, P. F. (2016). Cancer immunotherapy targeting neoantigens. Seminars in Immunology, 28(1), 22-27. doi:10.1016/j.smim.2015.11.002
- Bonifant, C. L., Jackson, H. J., Brentjens, R. J., & Curran, K. J. (2016). Toxicity and management in CAR T-cell therapy. Molecular Therapy - Oncolytics, 3, 16011. doi:10.1038/mto.2016.11
- Rodgers, D. T., Mazagova, M., Hampton, E. N., Cao, Y., Ramadoss, N. S., Hardy, I. R., Young, T. S. (2016). Switch-mediated activation and retargeting of CAR-T cells for B-cell malignancies. Proceedings of the National Academy of Sciences, 113(4). doi:10.1073/pnas.1524155113
- Cao, Y., Rodgers, D. T., Du, J., Ahmad, I., Hampton, E. N., Ma, J. S., Young, T. S. (2016). Design of Switchable Chimeric Antigen Receptor T Cells Targeting Breast Cancer. Angewandte Chemie, 128(26), 7646-7650. doi:10.1002/ange.201601902
- Fedorov, V. D., Themeli, M., & Sadelain, M. (2013). PD-1- and CTLA-4-Based Inhibitory Chimeric Antigen Receptors (iCARs) Divert Off-Target Immunotherapy Responses. Science Translational Medicine, 5(215). doi:10.1126/scitranslmed.3006597
- Diaconu, I., Ballard, B., Zhang, M., Chen, Y., West, J., Dotti, G., & Savoldo, B. (2017). Inducible Caspase-9 Selectively Modulates the Toxicities of CD19-Specific Chimeric Antigen Receptor-Modified T Cells. Molecular Therapy, 25(3), 580-592. doi:10.1016/j.ymthe.2017.01.011
- Sadikovic, B., Al-Romaih, K., Squire, J., & Zielenska, M. (2008). Cause and Consequences of Genetic and Epigenetic Alterations in Human Cancer. Current Genomics, 9(6), 394-408. doi:10.2174/138920208785699580
- Dagogo-Jack, I., & Shaw, A. T. (2017). Tumour heterogeneity and resistance to cancer therapies. Nature Reviews Clinical Oncology, 15(2), 81-94. doi:10.1038/nrclinonc.2017.166
- Meacham, C. E., & Morrison, S. J. (2013). Tumour heterogeneity and cancer cell plasticity. Nature, 501(7467), 328-337. doi:10.1038/nature12624
- Genßler, S., Burger, M. C., Zhang, C., Oelsner, S., Mildenberger, I., Wagner, M., . . . Wels, W. S. (2015). Dual targeting of glioblastoma with chimeric antigen receptor-engineered natural killer cells overcomes heterogeneity of target antigen expression and enhances antitumor activity and survival. OncoImmunology, 5(4). doi:10.1080/2162402x.2015.1119354
- Thomas, S., Baldan, V., Kokalaki, E., Righi, M., Sillibourne, J., Cordoba, S., Pule, M. (2017). A Dual Targeting Car-T Cell Approach For The Treatment Of B Cell Malignancies. Hematological Oncology, 35, 261-261. doi:10.1002/hon.2438_129
- Negrini, S., Gorgoulis, V. G., & Halazonetis, T. D. (2010). Genomic instability — an evolving hallmark of cancer. Nature Reviews Molecular Cell Biology, 11(3), 220-228. doi:10.1038/nrm2858
- Saridaki, Z. (2014). Prognostic and predictive significance of MSI in stages II/III colon cancer. World Journal of Gastroenterology, 20(22), 6809. doi:10.3748/wjg.v20.i22.6809
- Gatalica, Z., Vranic, S., Xiu, J., Swensen, J., & Reddy, S. (2016). High microsatellite instability (MSI-H) colorectal carcinoma: A brief review of predictive biomarkers in the era of personalized medicine. Familial Cancer, 15(3), 405-412. doi:10.1007/s10689-016-9884-6
- Walker, B. A., Wardell, C. P., Murison, A., Boyle, E. M., Begum, D. B., Dahir, N. M., Morgan, G. J. (2015). APOBEC family mutational signatures are associated with poor prognosis translocations in multiple myeloma. Nature Communications, 6(1). doi:10.1038/ncomms7997
- Walters, J. N., Ferraro, B., Duperret, E. K., Kraynyak, K. A., Chu, J., Saint-Fleur, A., Weiner, D. B. (2017). A Novel DNA Vaccine Platform Enhances Neo-antigen-like T Cell Responses against WT1 to Break Tolerance and Induce Anti-tumor Immunity. Molecular Therapy, 25(4), 976-988. doi:10.1016/j.ymthe.2017.01.022
- ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). Identifier NCT03412877. Administration of Autologous T-Cells Genetically Engineered to Express T-Cell Receptors Reactive Against Mutated Neoantigens in People with Metastatic Cancer. (n.d.). Cited 2018 June 22. Retrieved from https://clinicaltrials.gov/ct2/show/NCT03412877
- Mcclanahan, F., Riches, J. C., Miller, S., Day, W. P., Kotsiou, E., Neuberg, D., Gribben, J. G. (2015). Mechanisms of PD-L1/PD-1-mediated CD8 T-cell dysfunction in the context of aging-related immune defects in the E -TCL1 CLL mouse model. Blood, 126(2), 212-221. doi:10.1182/blood-2015-02-626754
- Zamani, M. R., Aslani, S., Salmaninejad, A., Javan, M. R., & Rezaei, N. (2016). PD-1/PD-L and autoimmunity: A growing relationship. Cellular Immunology, 310, 27-41. doi:10.1016/j.cellimm.2016.09.009
- Xiang, X., Yu, P., Long, D., Liao, X., Zhang, S., You, X., Li, L. (2018). Prognostic value of PD-L1 expression in patients with primary solid tumors. Oncotarget, 9(4). doi:10.18632/oncotarget.23580
- Zhu, J., Wen, H., Bi, R., Wu, Y., & Wu, X. (2017). Prognostic value of programmed death-ligand 1 (PD-L1) expression in ovarian clear cell carcinoma. Journal of Gynecologic Oncology, 28(6). doi:10.3802/jgo.2017.28.e77
- Balar, A. V., & Weber, J. S. (2017). PD-1 and PD-L1 antibodies in cancer: Current status and future directions. Cancer Immunology, Immunotherapy, 66(5), 551-564. doi:10.1007/s00262-017-1954-6
- Korman, A. J., Peggs, K. S., & Allison, J. P. (2006). Checkpoint Blockade in Cancer Immunotherapy. Advances in Immunology Cancer Immunotherapy, 297-339. doi:10.1016/s0065-2776(06)90008-x
- Pardoll, D. M. (2012). The blockade of immune checkpoints in cancer immunotherapy. Nature Reviews Cancer, 12(4), 252-264. doi:10.1038/nrc3239
- Kochenderfer, J. N., Somerville, R. P., Lu, T., Yang, J. C., Sherry, R. M., Feldman, S. A., Rosenberg, S. A. (2017). Long-Duration Complete Remissions of Diffuse Large B Cell Lymphoma after Anti-CD19 Chimeric Antigen Receptor T Cell Therapy. Molecular Therapy, 25(10), 2245-2253. doi:10.1016/j.ymthe.2017.07.004
- Brudno, J. N., Somerville, R. P., Shi, V., Rose, J. J., Halverson, D. C., Fowler, D. H., Kochenderfer, J. N. (2016). Allogeneic T Cells That Express an Anti-CD19 Chimeric Antigen Receptor Induce Remissions of B-Cell Malignancies That Progress After Allogeneic Hematopoietic Stem-Cell Transplantation Without Causing Graft-Versus-Host Disease. Journal of Clinical Oncology, 34(10), 1112-1121. doi:10.1200/jco.2015.64.5929
- John, L. B., Devaud, C., Duong, C. P., Yong, C. S., Beavis, P. A., Haynes, N. M., Darcy, P. K. (2013). Anti-PD-1 Antibody Therapy Potently Enhances the Eradication of Established Tumors By Gene-Modified T Cells. Clinical Cancer Research, 19(20), 5636-5646. doi:10.1158/1078-0432.ccr-13-0458
- ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). Identifier NCT03179007. CTLA-4 and PD-1 Antibodies Expressing MUC1-CAR-T Cells for MUC1 Positive Advanced Solid Tumor. (n.d.). Retrieved from https://clinicaltrials.gov/ct2/show/NCT03179007
- ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). Identifier NCT03182816. CTLA-4 and PD-1 Antibodies Expressing EGFR-CAR-T Cells for EGFR Positive Advanced Solid Tumor. (n.d.). Cited 2018 June 22. Retrieved from https://clinicaltrials.gov/ct2/show/NCT03182816
- ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). Identifier NCT03030001. PD-1 Antibody Expressing CAR T Cells for Mesothelin Positive Advanced Malignancies. (n.d.). Retrieved September 05, 2018, from https://clinicaltrials.gov/ct2/show/NCT03030001
- Liu, X., Ranganathan, R., Jiang, S., Fang, C., Sun, J., Kim, S., Moon, E. K. (2016). A Chimeric Switch-Receptor Targeting PD1 Augments the Efficacy of Second-Generation CAR T Cells in Advanced Solid Tumors. Cancer Research, 76(6), 1578-1590. doi:10.1158/0008-5472.can-15-2524
- Rupp, L. J., Schumann, K., Roybal, K. T., Gate, R. E., Ye, C. J., Lim, W. A., & Marson, A. (2017). CRISPR/Cas9-mediated PD-1 disruption enhances anti-tumor efficacy of human chimeric antigen receptor T cells. Scientific Reports, 7(1). doi:10.1038/s41598-017-00462-8
- Ligtenberg, M. A., Coaña, Y. P., Shmushkovich, T., Yoshimoto, Y., Truxova, I., Yang, Y., Kiessling, R. (2018). Self-Delivering RNAi Targeting PD-1 Improves Tumor-Specific T Cell Functionality for Adoptive Cell Therapy of Malignant Melanoma. Molecular Therapy, 26(6), 1482-1493. doi:10.1016/j.ymthe.2018.04.015
- Olson, B. M., & Mcneel, D. G. (2012). Antigen loss and tumor-mediated immunosuppression facilitate tumor recurrence. Expert Review of Vaccines, 11(11), 1315-1317. doi:10.1586/erv.12.107
- Giuliano, M., Schiff, R., Osborne, C. K., & Trivedi, M. V. (2011). Biological mechanisms and clinical implications of endocrine resistance in breast cancer. The Breast, 20. doi:10.1016/s0960-9776(11)70293-4
- Garrido, F., Ruiz-Cabello, F., Cabrera, T., Pérez-Villar, J. J., López-Botet, M., Duggan-Keen, M., & Stern, P. L. (1997). Implications for immunosurveillance of altered HLA class I phenotypes in human tumours. Immunology Today, 18(2), 89-95. doi:10.1016/s0167-5699(96)10075-x
- Seliger, B., Cabrera, T., Garrido, F., & Ferrone, S. (2002). HLA class I antigen abnormalities and immune escape by malignant cells. Seminars in Cancer Biology, 12(1), 3-13. doi:10.1006/scbi.2001.0404
- Atkins, D., Breuckmann, A., Schmahl, G. E., Binner, P., Ferrone, S., Krummenauer, F., Seliger, B. (2004). MHC class I antigen processing pathway defects, ras mutations and disease stage in colorectal carcinoma. International Journal of Cancer, 109(2), 265-273. doi:10.1002/ijc.11681
- Ritter, C., Fan, K., Paschen, A., Hardrup, S. R., Ferrone, S., Nghiem, P., Becker, J. C. (2017). Epigenetic priming restores the HLA class-I antigen processing machinery expression in Merkel cell carcinoma. Scientific Reports, 7(1). doi:10.1038/s41598-017-02608-0
- Koerner, J., Brunner, T., & Groettrup, M. (2017). Inhibition and deficiency of the immunoproteasome subunit LMP7 suppress the development and progression of colorectal carcinoma in mice. Oncotarget, 8(31). doi:10.18632/oncotarget.15141
- Glavinas, H., Krajcsi, P., Cserepes, J., & Sarkadi, B. (2004). The Role of ABC Transporters in Drug Resistance, Metabolism and Toxicity. Current Drug Delivery, 1(1), 27-42. doi:10.2174/1567201043480036
- Henle, A. M., Nassar, A., Puglisi-Knutson, D., Youssef, B., & Knutson, K. L. (2017). Downregulation of TAP1 and TAP2 in early stage breast cancer. Plos One, 12(11). doi:10.1371/journal.pone.0187323
- Ling, A., Löfgren-Burström, A., Larsson, P., Li, X., Wikberg, M. L., Öberg, Å, Palmqvist, R. (2017). TAP1 down-regulation elicits immune escape and poor prognosis in colorectal cancer. OncoImmunology, 6(11). doi:10.1080/2162402x.2017.1356143
- Fischer, J., Paret, C., Malki, K. E., Alt, F., Wingerter, A., Neu, M. A., Faber, J. (2017). CD19 Isoforms Enabling Resistance to CART-19 Immunotherapy Are Expressed in B-ALL Patients at Initial Diagnosis. Journal of Immunotherapy, 40(5), 187-195. doi:10.1097/cji.0000000000000169
- Hegde, M., Mukherjee, M., Grada, Z., Pignata, A., Landi, D., Navai, S. A., Ahmed, N. (2016). Tandem CAR T cells targeting HER2 and IL13Rα2 mitigate tumor antigen escape. Journal of Clinical Investigation, 126(8), 3036-3052. doi:10.1172/jci83416
- Gong, Y., Liu, Y., Ji, P., Hu, X., & Shao, Z. (2017). Impact of molecular subtypes on metastatic breast cancer patients: A SEER population-based study. Scientific Reports, 7(1). doi:10.1038/srep45411
- Palma, M. D., & Hanahan, D. (2012). The biology of personalized cancer medicine: Facing individual complexities underlying hallmark capabilities. Molecular Oncology, 6(2), 111-127. doi:10.1016/j.molonc.2012.01.011
- Zhou, J., Yan, Y., Guo, L., Ou, H., Tang, L. (2014). Distinct outcomes in patients with different molecular subtypes of inflammatory breast cancer. Saudi Med J, 35 (11): 1324-1330.
- Enck, P., Klosterhalfen, S., Weimer, K., Horing, B., & Zipfel, S. (2011). The placebo response in clinical trials: More questions than answers. Philosophical Transactions of the Royal Society B: Biological Sciences, 366(1572), 1889-1895. doi:10.1098/rstb.2010.0384
- Garnett, S. A., Martin, M., Jerusalem, G., Petruzelka, L., Torres, R., Bondarenko, I. N., Leo, A. D. (2013). Comparing duration of response and duration of clinical benefit between fulvestrant treatment groups in the CONFIRM trial: Application of new methodology. Breast Cancer Research and Treatment, 138(1), 149-155. doi:10.1007/s10549-012-2395-8
- Cross, D., & Burmester, J. K. (2004). The Promise of Molecular Profiling for Cancer Identification and Treatment. Clinical Medicine & Research, 2(3), 147-150. doi:10.3121/cmr.2.3.147
- Ioannidis, J. P. (2007). Is Molecular Profiling Ready for Use in Clinical Decision Making? The Oncologist, 12(3), 301-311. doi:10.1634/theoncologist.12-3-301
- Greco, F. A., Spigel, D. R., Yardley, D. A., Erlander, M. G., Ma, X., & Hainsworth, J. D. (2010). Molecular Profiling in Unknown Primary Cancer: Accuracy of Tissue of Origin Prediction. The Oncologist, 15(5), 500-506. doi:10.1634/theoncologist.2009-0328
- Niu, T., Chang, L-J., Yang, J., Liu, Y., ... Liu, T. (2015). Rescue of a terminally ill patient with chemo-refractory acute lymphoblastic leukemia carrying Bcr/Abl and TP53 mutations based on a 4th generation CD19 chimeric antigen receptor-engineered T (CAR-T) therapy. Blood, 126 (23): 5431.
- Cheng, D. T., Mitchell, T. N., Zehir, A., Shah, R. H., Benayed, R., Syed, A., Berger, M. F. (2015). Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets (MSK-IMPACT). The Journal of Molecular Diagnostics, 17(3), 251-264. doi:10.1016/j.jmoldx.2014.12.006
- Zehir, A., Benayed, R., Shah, R., Syed, A., Berger, M. (2017). Mutational landscape of metastatic cancer revealed from prospective clinical sequencing of 10,000 patients. Nat Med, 23 (6):703-713. doi: 10.1038/nm.4333
DOI: https://doi.org/10.24294/ti.v4.i2.1064
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