Lentiviral vectors in cancer immunotherapy

Papers of special note have been highlighted as: • of interest

References

• 1 Morgan RA, Dudley ME, Wunderlich JR et al. Cancer regression in patients after transfer of genetically engineered lymphocytes. Science 314(5796), 126–129 (2006).
  Medline CASGoogle Scholar
• 2 Gene therapy clinical trials worldwide. www.wiley.co.uk/genmed/clinical
  Google Scholar
• 3 Wilson JM. Adenoviruses as gene-delivery vehicles. N. Engl. J. Med. 334, 1185–1187 (1996)
  Medline CASGoogle Scholar
• 4 Janovitz T, Klein IA, Oliveira T et al. High-throughput sequencing reveals principles of adeno-associated virus serotype 2 integration. J. Virol. 87(15), 8559–8568 (2013).
  Medline CASGoogle Scholar
• 5 Dong JY, Fan PD, Frizzell RA. Quantitative analysis of the packaging capacity of recombinant adeno-associated virus. Hum. Gene Ther. 7(17), 2101–2112 (1996).
  Medline CASGoogle Scholar
• 6 Malim MH, Emerman M. HIV-1 accessory proteins – ensuring viral survival in a hostile environment. Cell Host Microbe 3(6), 388–398 (2008).
  Medline CASGoogle Scholar
• 7 Jones IM, Morikawa Y. The molecular basis of HIV capsid assembly. Rev. Med. Virol. 8(2), 87–95 (1998).
  Medline CASGoogle Scholar
• 8 Finkelshtein D, Werman A, Novick D, Barak S, Rubinstein M. LDL receptor and its family members serve as the cellular receptors for vesicular stomatitis virus. Proc. Natl Acad. Sci. USA 110(18), 7306–7311 (2013).
  Medline CASGoogle Scholar
• 9 Zennou V, Petit C, Guetard D, Nerhbass U, Montagnier L, Charneau P. HIV-1 genome nuclear import is mediated by a central DNA flap. Cell 101(2), 173–185 (2000).
  Medline CASGoogle Scholar
• 10 Palù G, Parolin C, Takeuchi Y, Pizzato M. Progress with retroviral gene vectors. Rev. Med. Virol. 10(3), 185–202 (2000).
  Medline CASGoogle Scholar
• 11 Watanabe S, Temin HM. Encapsidation sequences for spleen necrosis virus, an avian retrovirus, are between the 5’ long terminal repeat and the start of the gag gene. Proc. Natl Acad. Sci. USA 79(19), 5986–5990 (1982).
  Medline CASGoogle Scholar
• 12 Dull T, Zufferey R, Kelly M et al. A third-generation lentivirus vector with a conditional packaging system. J. Virol. 72(11), 8463–8471 (1998).
  Medline CASGoogle Scholar
• 13 Zufferey R, Nagy D, Mandel RJ, Naldini L, Trono D. Multiply attenuated lentiviral vector achieves efficient gene delivery in vivo. Nat. Biotechnol. 15(9), 871–875 (1997).
  Medline CASGoogle Scholar
• 14 Zufferey R, Dull T, Mandel RJ et al. Self-inactivating lentivirus vector for safe and efficient in vivo gene delivery. J. Virol. 72(12), 9873–9880 (1998).
  Medline CASGoogle Scholar
• 15 Miyoshi H, Blömer U, Takahashi M, Gage FH, Verma IM. Development of a self-inactivating lentivirus vector. J. Virol. 72(10), 8150–8157 (1998).
  Medline CASGoogle Scholar
• 16 Sirven A, Pflumio F, Zennou V et al. The human immunodeficiency virus type-1 central DNA flap is a crucial determinant for lentiviral vector nuclear import and gene transduction of human hematopoietic stem cells. Blood 96(13), 4103–4110 (2000).
  Medline CASGoogle Scholar
• 17 Zufferey R, Donello JE, Trono D, Hope TJ. Woodchuck hepatitis virus posttranscriptional regulatory element enhances expression of transgenes delivered by retroviral vectors. J. Virol. 73(4), 2886–2892 (1999).
  Medline CASGoogle Scholar
• 18 Barry SC, Harder B, Brzezinski M, Flint LY, Seppen J, Osborne WR. Lentivirus vectors encoding both central polypurine tract and posttranscriptional regulatory element provide enhanced transduction and transgene expression. Hum. Gene Ther. 12(9), 1103–1108 (2001).
  Medline CASGoogle Scholar
• 19 Gossen M, Freundlieb S, Bender G, Müller G, Hillen W, Bujard H. Transcriptional activation by tetracyclines in mammalian cells. Science 268(5218), 1766–1769 (1995).
  Medline CASGoogle Scholar
• 20 Cavazzana-Calvo M, Hacein-Bey S, de Saint Basile G et al. Gene therapy of human severe combined immunodeficiency (SCID)-X1 disease. Science 288(5466), 669–672 (2000).
  Medline CASGoogle Scholar
• 21 Cattoglio C, Facchini G, Sartori D et al. Hot spots of retroviral integration in human CD34⁺ hematopoietic cells. Blood 110(6), 1770–1778 (2007).
  Medline CASGoogle Scholar
• 22 Ronen K, Negre O, Roth S et al. Distribution of lentiviral vector integration sites in mice following therapeutic gene transfer to treat β-thalassemia. Mol. Ther. 19(7), 1273–1286 (2011).
  Medline CASGoogle Scholar
• 23 Rittelmeyer I, Rothe M, Brugman MH et al. Hepatic lentiviral gene transfer is associated with clonal selection, but not with tumor formation in serially transplanted rodents. Hepatology 58(1), 397–408 (2013).
  Medline CASGoogle Scholar
• 24 Philippe S, Sarkis C, Barkats M et al. Lentiviral vectors with a defective integrase allow efficient and sustained transgene expression in vitro and in vivo. Proc. Natl Acad. Sci. USA 103(47), 17684–17689 (2006).
  Medline CASGoogle Scholar
• 25 Yáñez-Muñoz RJ, Balaggan KS, MacNeil A et al. Effective gene therapy with nonintegrating lentiviral vectors. Nat. Med. 12(3), 348–353 (2006).
  Medline CASGoogle Scholar
• 26 Bayer M, Kantor B, Cockrell A et al. A large U3 deletion causes increased in vivo expression from a nonintegrating lentiviral vector. Mol. Ther. 16(12), 1968–1976 (2008).
  Medline CASGoogle Scholar
• 27 Cornu TI, Cathomen T. Targeted genome modifications using integrase-deficient lentiviral vectors. Mol. Ther. 15(12), 2107–2113 (2007).
  Medline CASGoogle Scholar
• 28 Kim Y, Kweon J, Kim A et al. A library of TAL effector nucleases spanning the human genome. Nat. Biotechnol. 31(3), 251–258 (2013).
  Medline CASGoogle Scholar
• 29 Karwacz K, Mukherjee S, Apolonia L et al. Nonintegrating lentivector vaccines stimulate prolonged T-cell and antibody responses and are effective in tumor therapy. J. Virol. 83(7), 3094–3103 (2009).
  Medline CASGoogle Scholar
• 30 Provasi E, Genovese P, Lombardo A et al. Editing T cell specificity towards leukemia by zinc finger nucleases and lentiviral gene transfer. Nat. Med. 18(5), 807–815 (2012).
  Medline CASGoogle Scholar
• 31 Jinek M, Chylinski K, Fonfara I, Hauer M, Doudna JA, Charpentier E. A programmable dual-RNA-guided DNA endonuclease in adaptive bacterial immunity. Science 337(6096), 816–821 (2012).
  Medline CASGoogle Scholar
• 32 Koike-Yusa H, Li Y, Tan EP, Velasco-Herrera Mdel C, Yusa K. Genome-wide recessive genetic screening in mammalian cells with a lentiviral CRISPR-guide RNA library. Nat. Biotechnol. 32(3), 267–273 (2014).
  Medline CASGoogle Scholar
• 33 Gilbert LA, Larson MH, Morsut L et al. CRISPR-mediated modular RNA-guided regulation of transcription in eukaryotes. Cell 154(2), 442–451 (2013).
  Medline CASGoogle Scholar
• 34 Fu Y, Foden JA, Khayter C et al. High-frequency off-target mutagenesis induced by CRISPR-Cas nucleases in human cells. Nat. Biotechnol. 9, 822–826 (2013).
  Google Scholar
• 35 Hsu PD, Scott DA, Weinstein JA et al. DNA targeting specificity of RNA-guided Cas9 nucleases. Nat. Biotechnol. 31, 827–832 (2013).
  Medline CASGoogle Scholar
• 36 Pattanayak V, Lin S, Guilinger JP, Ma E, Doudna JA, Liu DR. High-throughput profiling of off-target DNA cleavage reveals RNA-programmed Cas9 nuclease specificity. Nat. Biotechnol. 31, 839–843 (2013).
  Medline CASGoogle Scholar
• 37 Cong L, Ran FA, Cox D et al. Multiplex genome engineering using CRISPR/Cas systems. Science 339, 819–823 (2013).
  Medline CASGoogle Scholar
• 38 Kim E, Kim S, Kim DH, Choi BS, Choi IY, Kim JS. Precision genome engineering with programmable DNA-nicking enzymes. Genome Res. 22(7), 1327–1333 (2012).
  Medline CASGoogle Scholar
• 39 Wang J, Friedman G, Doyon Y et al. Targeted gene addition to a predetermined site in the human genome using a ZFN-based nicking enzyme. Genome Res. 22(7), 1316–1326 (2012).
  MedlineGoogle Scholar
• 40 Ramirez CL, Certo MT, Mussolino C et al. Engineered zinc finger nickases induce homology-directed repair with reduced mutagenic effects. Nucleic Acids Res. 40(12), 5560–5568 (2012).
  Medline CASGoogle Scholar
• 41 Holkers M, Maggio I, Liu J et al. Differential integrity of TALE nuclease genes following adenoviral and lentiviral vector gene transfer into human cells. Nucleic Acids Res. 41(5), e63 (2013).
  Medline CASGoogle Scholar
• 42 Black ME, Newcomb TG, Wilson HM, Loeb LA. Creation of drug-specific herpes simplex virus type 1 thymidine kinase mutants for gene therapy. Proc. Natl Acad. Sci. USA 93(8), 3525–3529 (1996).
  Medline CASGoogle Scholar
• 43 Casucci M, Bondanza A. Suicide gene therapy to increase the safety of chimeric antigen receptor-redirected T lymphocytes. J. Cancer 2, 378–382 (2001).
  Google Scholar
• 44 Berger C, Flowers ME, Warren EH, Riddell SR. Analysis of transgene-specific immune responses that limit the in vivo persistence of adoptively transferred HSV-TK-modified donor T cells after allogeneic hematopoietic cell transplantation. Blood 107(6), 2294–2302 (2006).
  Medline CASGoogle Scholar
• 45 Sato T, Neschadim A, Konrad AM, Fowler DH, Lavie A, Medin JA. Engineered human tmpk/AZT as a novel enzyme/prodrug axis for suicide gene therapy. Mol. Ther. 15(5), 962–970 (2007).• This paper presents the development of a novel cell-fate control (aka ‘suicide’) system based on a minimally modified human kinase that converts the prodrug azidothymidine to a cytotoxic version. Prodrug conversion is efficient and cell killing is effected through DNA chain termination and mitochondria disruption effects.
  Medline CASGoogle Scholar
• 46 Neschadim A, Wang JC, Sato T, Fowler DH, Lavie A, Medin JA. Cell fate control gene therapy based on engineered variants of human deoxycytidine kinase. Mol. Ther. 20(5), 1002–1013 (2012).• A human dCK based cell-fate control (aka ‘suicide’) system is described here, which is capable of inducing apoptosis in transduced cells exposed to a variety of normally nontoxic prodrugs such as bromovinyl-deoxyuridine or l-deoxythymidine. As this modified safety enzyme adds the first phosphate to the prodrug, it is also effective in imaging studies.
  Medline CASGoogle Scholar
• 47 Scaife M, Pacienza N, Au BC et al. Engineered human Tmpk fused with truncated cell-surface markers: versatile cell-fate control safety cassettes. Gene Ther. 20(1), 24–34 (2013).
  Medline CASGoogle Scholar
• 48 Banchereau J, Steinman RM. Dendritic cells and the control of immunity. Nature 392(6673), 245–252 (1998).
  Medline CASGoogle Scholar
• 49 Nestle FO, Alijagic S, Gilliet M et al. Vaccination of melanoma patients with peptide or tumor lysate-pulsed dendritic cells. Nat. Med. 4(3), 328–332 (1998).
  Medline CASGoogle Scholar
• 50 Dawson NA, Roesch EE. Sipuleucel-T and immunotherapy in the treatment of prostate cancer. Expert Opin. Biol. Ther. 14(5), 709–719 (2014).
  Medline CASGoogle Scholar
• 51 Breckpot K, Dullaers M, Bonehill A et al. Lentivirally transduced dendritic cells as a tool for cancer immunotherapy. J. Gene Med. 5(8), 654–667 (2003).
  Medline CASGoogle Scholar
• 52 Jeon, MS, Atfield, A., Venuprasad, K et al. Essential role of the E3 ubiquitin ligase Cbl-b in T cell anergy induction. Immunity 21(2), 167–177 (2004).
  Medline CASGoogle Scholar
• 53 Nurieva, R., Thomas, S., Nguyen, T et al. T-cell tolerance or function is determined by combinatorial costimulatory signals. EMBO J. 25(11), 2623–2633 (2006).
  Medline CASGoogle Scholar
• 54 Curtsinger, JM, Johnson, CM, Mescher, MF. CD8 T cell clonal expansion and development of effector function require prolonged exposure to antigen, costimulation, and signal 3 cytokine. J. Immunol. 171(10), 5165–5171 (2003).
  Medline CASGoogle Scholar
• 55 Karwacz, K, Bricogne, C, MacDonald, D et al. PD-L1 co-stimulation contributes to ligand-induced T cell receptor down-modulation on CD8(⁺) T cells. EMBO Mol. Med. 3(10), 581–592 (2011).
  Medline CASGoogle Scholar
• 56 Pen, JJ, Keersmaecker, BD, Heirman, C et al. (2014). Interference with PD-L1/PD-1 co-stimulation during antigen presentation enhances the multifunctionality of antigen-specific T cells. Gene Ther. 21(3), 262–271 (2014).
  Medline CASGoogle Scholar
• 57 Fife, BT, Pauken, KE, Eagar, TN et al. Interactions between PD-1 and PD-L1 promote tolerance by blocking the TCR-induced stop signal. Nat. Immunol. 10(11), U1185–U1170 (2009).
  Medline CASGoogle Scholar
• 58 Escors, D, Lopes, L, Lin, R et al. Targeting dendritic cell signaling to regulate the response to immunization. Blood 111(6), 3050–3061 (2008).
  Medline CASGoogle Scholar
• 59 Felizardo TC, Wang JCM, Mcgray RA et al. Differential immune responses mediated by adenovirus- and lentivirus-transduced DCs in a HER-2/neu overexpressing tumor model. Gene Ther. 18(10), 986–995 (2011).
  Medline CASGoogle Scholar
• 60 Brown BD, Sitia G, Annoni A et al. In vivo administration of lentiviral vectors triggers a type I interferon response that restricts hepatocyte gene transfer and promotes vector clearance. Blood 109(7), 2797–2805 (2007).
  Medline CASGoogle Scholar
• 61 Breckpot K, Escors D, Arce F et al. HIV-1 lentiviral vector immunogenicity is mediated by Toll-Like Receptor 3 (TLR3) and TLR7. J. Virol. 84(11), 5627–5636 (2010).
  Medline CASGoogle Scholar
• 62 Metharom P, Ellem KA, Schmidt C, Wei MQ. Lentiviral vector-mediated tyrosinase-related protein 2 gene transfer to dendritic cells for the therapy of melanoma. Hum. Gene Ther. 12(18), 2203–2213 (2001).
  Medline CASGoogle Scholar
• 63 Metharom P, Ellem KA, Wei MQ. Gene transfer to dendritic cells induced a protective immunity against melanoma. Cell Mol. Immunol. 2(4), 281–288 (2005).
  Medline CASGoogle Scholar
• 64 Koya RC, Kimura T, Ribas A et al. Lentiviral vector-mediated autonomous differentiation of mouse bone marrow cells into immunologically potent dendritic cell vaccines. Mol. Ther. 15(5), 971–980 (2007).
  Medline CASGoogle Scholar
• 65 Wang B, He J, Liu C, Chang LJ. An effective cancer vaccine modality: Lentiviral modification of dendritic cells expressing multiple cancer-specific antigens. Vaccine 24(17), 3477–3489 (2006).
  Medline CASGoogle Scholar
• 66 Mossoba ME, Walia JS, Rasaiah VI et al. Tumor protection following vaccination with low doses of lentivirally transduced DCs expressing the self-antigen erbB2. Mol. Ther. 16(3), 607–617 (2008).
  Medline CASGoogle Scholar
• 67 Xiao L, Joo K-I, Lim M, Wang P. Dendritic cell directed vaccination with a lentivector encoding PSCA for prostate cancer in mice. PLoS ONE 7(11) e48866, (2012).• Describes lentiviral vector (LV)-transduced dendritic cells (DCs) engineered to express the prostate cancer tumor-associated antigen PSCA. Such LV transduced DCs were able to induce a cancer-specific immune response and provide significant tumor suppression.
  Medline CASGoogle Scholar
• 68 Romani N, Gruner S, Brang D et al. Proliferating dendritic cell progenitors in human blood. J. Exp. Med. 180(1), 83–93 (1994).
  Medline CASGoogle Scholar
• 69 Sallusto F, Lanzavecchia A. Efficient presentation of soluble-antigen by cultured human dendritic cells is maintained by granulocyte-macrophage colony-stimulating factor plus interleukin-4 and down-regulated by Tumor-Necrosis-Factor-alpha. J. Exp. Med. 179(4), 1109–1118 (1994).
  Medline CASGoogle Scholar
• 70 Reid CDL, Stackpoole A, Meager A, Tikerpae J. Interactions of tumor-necrosis-factor with granulocyte-macrophage colony-stimulating factor and other cytokines in the regulation of dendritic cell-growth in vitro from early bipotent CD34⁺ progenitors in human bone-marrow. J. Immunol. 149(8), 2681–2688 (1992).
  Medline CASGoogle Scholar
• 71 Salmon P, Arrighi JF, Piguet V et al. Transduction of CD34⁺ cells with lentiviral vectors enables the production of large quantities of transgene-expressing immature and mature dendritic cells. J. Gene Med. 3(4), 311–320 (2001).
  Medline CASGoogle Scholar
• 72 Chinnasamy N, Chinnasamy D, Toso JF et al. Efficient gene transfer to human peripheral blood monocyte-derived dendritic cells using human immunodeficiency virus type 1-based lentiviral vectors. Hum. Gene Ther. 11(13), 1901–1909 (2000).
  Medline CASGoogle Scholar
• 73 Senju S, Haruta M, Matsumura K et al. Generation of dendritic cells and macrophages from human induced pluripotent stem cells aiming at cell therapy. Gene Ther. 18(9), 874–883 (2011).• Describes the LV-mediated transformation of donor dermal fibroblasts by transduction of OCT3/4, SOX2, c-MYC and Klf4 transgenes and their subsequent differentiation into functional DCs.
  Medline CASGoogle Scholar
• 74 Zhan XC, Dravid G, Ye ZH et al. Functional antigen-presenting leucocytes derived from human embryonic stem cells in vitro. Lancet 364(9429), 163–171 (2004).
  MedlineGoogle Scholar
• 75 Kamath AT, Henri S, Battye F, Tough DF, Shortman K. Developmental kinetics and lifespan of dendritic cells in mouse lymphoid organs. Blood 100(5), 1734–1741 (2002).
  Medline CASGoogle Scholar
• 76 Wang JCM, Felizardo TC, Au BCY, Fowler DH, Dekaban GA, Medin JA. Engineering lentiviral vectors for modulation of dendritic cell apoptotic pathways. Virol. J. 10, 240 (2013).
  Medline CASGoogle Scholar
• 77 He YK, Zhang JY, Donahue C, Falo LD. Skin-derived dendritic cells induce potent CD8(⁺) T cell immunity in recombinant lentivector-mediated genetic immunization. Immunity 24(5), 643–656 (2006).
  Medline CASGoogle Scholar
• 78 Negri DRM, Michelini Z, Baroncelli S et al. Successful immunization with a single injection of non-integrating lentiviral vector. Mol. Ther. 15(9), 1716–1723 (2007).
  Medline CASGoogle Scholar
• 79 Dai B, Yang L, Yang H, Hu B, Baltimore D, Wang P. HIV-1 Gag-specific immunity induced by a lentivector-based vaccine directed to dendritic cells. Proc. Natl Acad. Sci. USA 106(48), 20382–20387 (2009).
  Medline CASGoogle Scholar
• 80 Hirano N, Takahashi T, Ohtake S et al. Expression of costimulatory molecules in human leukemias. Leukemia 10(7), 1168–1176 (1996).
  Medline CASGoogle Scholar
• 81 Brunda MJ, Luistro L, Warrier RR et al. Anti-tumor and anti-metastatic activity of interleukin-12 against murine tumors. J. Exp. Med. 178(4), 1223–1230 (1993).
  Medline CASGoogle Scholar
• 82 Cohen J. IL-12 deaths: explanation and a puzzle. Science 270(5238), 908–908 (1995).
  Medline CASGoogle Scholar
• 83 Gollob JA, Mier JW, Veenstra K et al. Phase I trial of twice-weekly intravenous interleukin 12 in patients with metastatic renal cell cancer or malignant melanoma: Ability to maintain IFN-gamma induction is associated with clinical response. Clin. Cancer Res. 6(5), 1678–1692 (2000).
  Medline CASGoogle Scholar
• 84 Haicheur N, Escudier B, Dorval T et al. Cytokines and soluble cytokine receptor induction after IL-12 administration in cancer patients. Clin. Exp. Immunol. 119(1), 28–37 (2000).
  Medline CASGoogle Scholar
• 85 Portielje JEA, Lamers CHJ, Kruit WHJ et al. Repeated administrations of interleukin (IL)-12 are associated with persistently elevated plasma levels of IL-10 and declining IFN-gamma, tumor necrosis factor-alpha, IL-6, and IL-8 responses. Clin. Cancer Res. 9(1), 76–83 (2003).
  Medline CASGoogle Scholar
• 86 Pizzoferrato E, Chu NR, Hawley TS et al. Enhanced immunogenicity of B cell lymphoma genetically engineered to express both B7–1 and interleukin-12. Hum. Gene Ther. 8(18), 2217–2228 (1997).
  Medline CASGoogle Scholar
• 87 Labbe A, Nelles M, Walia J et al. IL-12 immunotherapy of murine leukaemia: comparison of systemic versus gene modified cell therapy. J. Cell Mol. Med. 13(8B), 1962–1976 (2009).• Describes the how leukemia cells themselves can be turned into anticancer vaccines by LV-mediated transduction of the cDNA encoding a fusion form of IL-12 subunits. Importantly, here it was shown that what is vital to the success of this approach is the threshold of fused IL-12 produced by the transduced tumor cells; above a certain level all animals were protected from tumor challenge, below that threshold no animals were protected.
  MedlineGoogle Scholar
• 88 Wei LZ, Xu Y, Nelles ME et al. Localized interleukin-12 delivery for immunotherapy of solid tumours. J. Cell Mol. Med. 17(11), 1465–1474 (2013).
  Medline CASGoogle Scholar
• 89 Stripecke R, Cardoso AA, Pepper KA et al. Lentiviral vectors for efficient delivery of CD80 and granulocyte-macrophage-colony-stimulating factor in human acute lymphoblastic leukemia and acute myeloid leukemia cells to induce anti-leukemic immune responses. Blood 96(4), 1317–1326 (2000).
  Medline CASGoogle Scholar
• 90 Chan L, Hardwick N, Darling D et al. IL-2/B7.1 (CD80) fusagene transduction of AML blasts by a self-inactivating lentiviral vector stimulates T cell responses in vitro: a strategy to generate whole cell vaccines for AML. Mol. Ther. 11(1), 120–131 (2005).
  Medline CASGoogle Scholar
• 91 Cortes JE, Kantarjian HM, O'Brien S et al. A pilot study of interleukin-2 for adult patients with acute myelogenous leukemia in first complete remission. Cancer 85(7), 1506–1513 (1999).
  Medline CASGoogle Scholar
• 92 Suhoski MM, Golovina TN, Aqui NA et al. Engineering artificial antigen-presenting cells to express a diverse array of co-stimulatory molecules. Mol. Ther. 15(5), 981–988 (2007).
  Medline CASGoogle Scholar
• 93 Dembic Z, Haas W, Weiss S et al. Transfer of specificity by murine alpha-T-cell and beta-T-cell receptor genes. Nature 320(6059), 232–238 (1986).
  Medline CASGoogle Scholar
• 94 Yang S, Cohen CJ, Peng PD et al. Development of optimal bicistronic lentiviral vectors facilitates high-level TCR gene expression and robust tumor cell recognition. Gene Ther. 15(21), 1411–1423 (2008).
  Medline CASGoogle Scholar
• 95 Clinicaltrials.gov NCT01795976. https://clinicaltrials.gov/ct2/show/NCT01795976
  Google Scholar
• 96 Clinicaltrials.gov NCT00910650. https://clinicaltrials.gov/ct2/show/NCT00910650
  Google Scholar
• 97 Bendle GM, Linnemann C, Hooijkaas AI et al. Lethal graft-versus-host disease in mouse models of T cell receptor gene therapy. Nat. Med. 16(5), 565–570 (2010).
  Medline CASGoogle Scholar
• 98 Porter DL, Levine BL, Kalos M, Bagg A, June CH. Chimeric antigen receptor-modified T cells in chronic lymphoid leukemia. N. Engl. J. Med. 365(8), 725–733 (2011).• Describes the ability of a CD19-directed chimeric antigen receptor in autologous T cells to treat patients with chronic lymphocytic leukemia. Chimeric antigen receptor T cells were able to provide a robust and specific immune response against CD19+ B-cell malignancies, clearing them from patients.
  Medline CASGoogle Scholar
• 99 Kochenderfer JN, Dudley ME, Feldman SA et al. B-cell depletion and remissions of malignancy along with cytokine-associated toxicity in a clinical trial of anti-CD19 chimeric-antigen-receptor-transduced T cells. Blood 119(12), 2709–2720 (2012).
  Medline CASGoogle Scholar
• 100 Finney HM, Akbar AN, Lawson ADG. Activation of resting human primary T cells with chimeric receptors: Costimulation from CD28, inducible costimulator, CD134, and CD137 in series with signals from the TCR zeta chain. J. Immunol. 172(1), 104–113 (2004).
  Medline CASGoogle Scholar
• 101 Imai C, Mihara K, Andreansky M et al. Chimeric receptors with 4-1BB signaling capacity provoke potent cytotoxicity against acute lymphoblastic leukemia. Leukemia 18(4), 676–684 (2004).
  Medline CASGoogle Scholar
• 102 Eshhar Z, Waks T, Gross G, Schindler DG. Specific activation and targeting of cytotoxic lymphocytes through chimeric single chains consisting of antibody-binding domains and the gamma-subunit or zeta-subunit of the immunoglobulin and T-cell receptors. Proc. Natl Acad. Sci. USA 90(2), 720–724 (1993).
  Medline CASGoogle Scholar
• 103 Boissel L, Betancur-Boissel M, Lu W et al. Retargeting NK-92 cells by means of CD19-and CD20-specific chimeric antigen receptors compares favorably with antibody-dependent cellular cytotoxicity. Oncoimmunology 2(10), e26527 (2013).
  MedlineGoogle Scholar
• 104 Frigault MJ, June CH. Predicting cytokine storms: it's about density. Blood 118(26), 6724–6726 (2011).
  Medline CASGoogle Scholar
• 105 Di Stasi A, Tey S-K, Dotti G et al. Inducible apoptosis as a safety switch for adoptive cell therapy. N. Engl. J. Med. 365(18), 1673–1683 (2011).
  Medline CASGoogle Scholar
• 106 Barrett DM, Zhao Y, Liu X et al. Treatment of advanced leukemia in mice with mRNA engineered T cells. Hum. Gene Ther. 22(12), 1575–1586 (2011).
  Medline CASGoogle Scholar
• 107 Maus MV, Haas AR, Beatty GL et al. T cells expressing chimeric antigen receptors can cause anaphylaxis in humans. Cancer Immunol. Res. 1(1), 26–31 (2013).
  CASGoogle Scholar