CAR-T Therapy for Solid Tumors: Development of New Strategies

Samuel D. Bernal

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.


Keywords


cancer immunotherapy; chimeric antigen receptor T cell therapy; lymphoma; solid tumors; cancer molecular profiling

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References


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: http://dx.doi.org/10.24294/ti.v2.i3.1064

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