Of CARs and TRUCKs: Chimeric antigen receptor (CAR) T cells engineered with an inducible cytokine to modulate the tumor stroma

Immunological Reviews

Volumn 257, Issue 1, 2014, Pages 83-90

  Chmielewski, Markus ^a,b   Hombach, Andreas A ^a,b   Abken, Hinrich ^a,b  

^a UNIVERSITY OF COLOGNE   (Germany)

^b UNIVERSITY HOSPITAL OF COLOGNE   (Germany)

Author keywords

Adoptive cell therapy; Chimeric antigen receptor; IL 12; Inducible cytokine; Innate immunity; Stroma; T cell

Indexed keywords

CHIMERIC ANTIGEN RECEPTOR; GAMMA INTERFERON; INTERLEUKIN 12; INTERLEUKIN 23; INTERLEUKIN 27; INTERLEUKIN 4; INTERLEUKIN 5; RECOMBINANT INTERLEUKIN 12; T LYMPHOCYTE RECEPTOR; TUMOR NECROSIS FACTOR ALPHA; UNCLASSIFIED DRUG;

ADOPTIVE IMMUNOTHERAPY; ADOPTIVE TRANSFER; ANTIGEN SPECIFICITY; APOPTOSIS; ARTICLE; CANCER CELL; CELL DIFFERENTIATION; CELL ENGINEERING; CELL THERAPY; CYTOKINE PRODUCTION; CYTOKINE RELEASE; HUMAN; IMMUNOSUPPRESSIVE TREATMENT; INNATE IMMUNITY; MEMORY T LYMPHOCYTE; NONHUMAN; PHENOTYPE; PRIORITY JOURNAL; SOLID TUMOR; STROMA; SUPPRESSOR CELL; T LYMPHOCYTE ACTIVATION; TUMOR ASSOCIATED LEUKOCYTE;

ADOPTIVE CELL THERAPY; CHIMERIC ANTIGEN RECEPTOR; IL-12; INDUCIBLE CYTOKINE; INNATE IMMUNITY; STROMA; T CELL;

ANIMALS; CYTOKINES; CYTOTOXICITY, IMMUNOLOGIC; HUMANS; IMMUNITY, INNATE; IMMUNOLOGIC FACTORS; IMMUNOMODULATION; IMMUNOTHERAPY, ADOPTIVE; INTERLEUKIN-12; NEOPLASMS; RECEPTORS, ANTIGEN, T-CELL; RECOMBINANT FUSION PROTEINS; STROMAL CELLS; T-LYMPHOCYTE SUBSETS;

EID: 84890179288     PISSN: 01052896     EISSN: 1600065X     Source Type: Journal    
DOI: 10.1111/imr.12125     Document Type: Article

References (62)

1. Rosenberg SA, et al. Durable complete responses in heavily pretreated patients with metastatic melanoma using T-cell transfer immunotherapy. Clin Cancer Res 2011;17:4550-4557.
2. Eshhar Z. The T-body approach: redirecting T cells with antibody specificity. Handb Exp Pharmacol 2008;181:329-42.
3. Bridgeman JS, Hawkins RE, Hombach AA, Abken H, Gilham DE. Building better chimeric antigen receptors for adoptive T cell therapy. Curr Gene Ther 2010;10:77-90.
4. Hombach AA, Abken H. Costimulation by chimeric antigen receptors revisited the T cell antitumor response benefits from combined CD28-OX40 signalling. Int J Cancer 2011;129:2935-2944.
5. Hoyos V, et al. Engineering CD19-specific T lymphocytes with interleukin-15 and a suicide gene to enhance their anti-lymphoma/leukemia effects and safety. Leukemia 2010;24:1160-1170.
6. Grupp SA, et al. Chimeric antigen receptor-modified T cells for acute lymphoid leukemia. N Engl J Med 2013;368:1509-18.
7. Kalos M, et al. T cells with chimeric antigen receptors have potent antitumor effects and can establish memory in patients with advanced leukemia. Sci Transl Med 2011;3:95ra73.
8. Brentjens RJ, et al. CD19-targeted T cells rapidly induce molecular remissions in adults with chemotherapy-refractory acute lymphoblastic leukemia. Sci Transl Med 2013;5:177ra38.
9. Förster A, et al. Anti-Fas/CD95 and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) differentially regulate apoptosis in normal and neoplastic human basophils. Leuk Lymphoma 2013;54:835-842.
10. Croci DO, Zacarías Fluck MF, Rico MJ, Matar P, Rabinovich GA, Scharovsky OG. Dynamic cross-talk between tumor and immune cells in orchestrating the immunosuppressive network at the tumor microenvironment. Cancer Immunol Immunother 2007;56:1687-1700.
11. Zitvogel L, Tesniere A, Kroemer G. Cancer despite immunosurveillance: immunoselection and immunosubversion. Nat Rev Immunol 2006;6:715-727.
12. Chmielewski M, Hombach A, Heuser C, Adams GP, Abken H. T cell activation by antibody-like immunoreceptors: increase in affinity of the single-chain fragment domain above threshold does not increase T cell activation against antigen-positive target cells but decreases selectivity. J Immunol 2004;173:7647-7653.
13. Terakura S, Yamamoto TN, Gardner RA, Turtle CJ, Jensen MC, Riddell SR. Generation of CD19-chimeric antigen receptor modified CD8+ T cells derived from virus-specific central memory T cells. Blood 2012;119:72-82.
14. Milone MC, et al. Chimeric receptors containing CD137 signal transduction domains mediate enhanced survival of T cells and increased antileukemic efficacy in vivo. Mol Ther 2009;17:1453-1464.
15. Chmielewski M, Kopecky C, Hombach AA, Abken H. IL-12 release by engineered T cells expressing chimeric antigen receptors can effectively Muster an antigen-independent macrophage response on tumor cells that have shut down tumor antigen expression. Cancer Res 2011;71:5697-5706.
16. Pegram HJ, et al. Tumor-targeted T cells modified to secrete IL-12 eradicate systemic tumors without need for prior conditioning. Blood 2012;119:4133-4141.
17. Kerkar SP, et al. Tumor-specific CD8+ T cells expressing interleukin-12 eradicate established cancers in lymphodepleted hosts. Cancer Res 2010;70:6725-6734.
18. Kerkar SP, et al. IL-12 triggers a programmatic change in dysfunctional myeloid-derived cells within mouse tumors. J Clin Invest 2011;121:4746-4757.
19. Trinchieri G, Pflanz S, Kastelein RA. The IL-12 family of heterodimeric cytokines: new players in the regulation of T cell responses. Immunity 2003;19:641-644.
20. Hung K, Hayashi R, Lafond-Walker A, Lowenstein C, Pardoll D, Levitsky H. The central role of CD4+ T cells in the antitumor immune response. J Exp Med 1998;188:2357-2368.
21. Tatsumi T, et al. Intratumoral delivery of dendritic cells engineered to secrete both interleukin (IL)-12 and IL-18 effectively treats local and distant disease in association with broadly reactive Tc1-type immunity. Cancer Res 2003;63:6378-6386.
22. Hsieh CS, Macatonia SE, Tripp CS, Wolf SF, O'Garra A, Murphy KM. Development of TH1 CD4+ T cells through IL-12 produced by Listeria-induced macrophages. Science 1993;260:547-549.
23. Wesa A, Kalinski P, Kirkwood JM, Tatsumi T, Storkus WJ. Polarized type-1 dendritic cells (DC1) producing high levels of IL-12 family members rescue patient TH1-type antimelanoma CD4+ T cell responses in vitro. J Immunother 2007;30:75-82.
24. Yoo JK, Cho JH, Lee SW, Sung YC. IL-12 provides proliferation and survival signals to murine CD4+ T cells through phosphatidylinositol 3-kinase/Akt signaling pathway. J Immunol 2002;169:3637-3643.
25. Curtsinger JM, Lins DC, Mescher MF. Signal 3 determines tolerance versus full activation of naive CD8 T cells: dissociating proliferation and development of effector function. J Exp Med 2003;197:1141-1151.
26. Kalinski P, Hilkens CM, Wierenga EA, Kapsenberg ML. T-cell priming by type-1 and type-2 polarized dendritic cells: the concept of a third signal. Immunol Today 1999;20:561-567.
27. Coughlin CM, et al. Interleukin-12 and interleukin-18 synergistically induce murine tumor regression which involves inhibition of angiogenesis. J Clin Invest 1998;101:1441-1452.
28. Trinchieri G. Interleukin-12 and the regulation of innate resistance and adaptive immunity. Nat Rev Immunol 2003;3:133-146.
29. Galon J, et al. Type, density, and location of immune cells within human colorectal tumors predict clinical outcome. Science 2006;313:1960-1964.
30. Mortarini R, et al. Peripheral burst of tumor-specific cytotoxic T lymphocytes and infiltration of metastatic lesions by memory CD8+ T cells in melanoma patients receiving interleukin 12. Cancer Res 2000;60:3559-3568.
31. van Herpen CM, et al. Intratumoral recombinant human interleukin-12 administration in head and neck squamous cell carcinoma patients modifies locoregional lymph node architecture and induces natural killer cell infiltration in the primary tumor. Clin Cancer Res 2005;11:1899-1909.
32. Car BD, Eng VM, Lipman JM, Anderson TD. The toxicology of interleukin-12: a review. Toxicol Pathol 1999;27:58-63.
33. Simpson-Abelson MR, et al. IL-12 delivered intratumorally by multilamellar liposomes reactivates memory T cells in human tumor microenvironments. Clin Immunol 2009;132:71-82.
34. Cui J, et al. Requirement for Valpha14 NKT cells in IL-12-mediated rejection of tumors. Science 1997;278:1623-1626.
35. Kang WK, et al. Interleukin 12 gene therapy of cancer by peritumoral injection of transduced autologous fibroblasts: outcome of a phase I study. Hum Gene Ther 2001;12:671-684.
36. Sun Y, Jurgovsky K, Moller P. Vaccination with IL-12 gene-modified autologous melanoma cells: preclinical results and a first clinical phase I study. Gene Ther 1998;5:481-490.
37. Heinzerling L, et al. Intratumoral injection of DNA encoding human interleukin-12 into patients with metastatic melanoma: clinical efficacy. Hum Gene Ther 2005;16:35-48.
38. Curti A, Parenza M, Colombo MP. Autologous and MHC class I-negative allogeneic tumor cells secreting IL-12 together cure disseminated A20 lymphoma. Blood 2003;101:568-575.
39. Eisenring M, vom Berg J, Kristiansen G, Saller E, Becher B. IL-12 initiates tumor rejection via lymphoid tissue-inducer cells bearing the natural cytotoxicity receptor NKp46. Nat Immunol 2010;11:1030-1038.
40. Cavallo F, et al. Antitumor efficacy of adenocarcinoma cells engineered to produce interleukin 12 (IL-12) or other cytokines compared with exogenous IL-12. J Natl Cancer Inst 1997;89:1049-1058.
41. Zhang L, et al. Improving adoptive T cell therapy by targeting and controlling IL-12 expression to the tumor environment. Mol Ther 2011;19:751-759.
42. Pritchard MT, Wolf SF, Kraybill WF, Repasky EA. The anti-tumor effect of interleukin-12 is enhanced by mild (fever-range) thermal therapy. Immunol Invest 2005;34:361-380.
43. Wagner HJ, et al. A strategy for treatment of Epstein-Barr virus-positive Hodgkin's disease by targeting interleukin 12 to the tumor environment using tumor antigen-specific T cells. Cancer Gene Ther 2004;11:81-91.
44. Fan H, Walters CS, Dunston GM, Tackey R. IL-12 plays a significant role in the apoptosis of human T cells in the absence of antigenic stimulation. Cytokine 2002;19:126-137.
45. Mehrotra PT, Wu D, Crim JA, Mostowski HS, Siegel JP. Effects of IL-12 on the generation of cytotoxic activity in human CD8+ T lymphocytes. J Immunol 1993;151:2444-2452.
46. Dowell AC, Oldham KA, Bhatt RI, Lee SP, Searle PF. Long-term proliferation of functional human NK cells, with conversion of CD56(dim) NK cells to a CD56 (bright) phenotype, induced by carcinoma cells co-expressing 4-1BBL and IL-12. Cancer Immunol Immunother 2012;61:615-28.
47. Díaz-Montero CM, et al. Synergy of brief activation of CD8 T-cells in the presence of IL-12 and adoptive transfer into lymphopenic hosts promotes tumor clearance and anti-tumor memory. Am J Cancer Res 2011;1:882-896.
48. Lu T, et al. Tumor-infiltrating myeloid cells induce tumor cell resistance to cytotoxic T cells in mice. J Clin Invest 2011;121:4015-4029.
49. Spiotto MT, Rowley DA, Schreiber H. Bystander elimination of antigen loss variants in established tumors. Nat Med 2004;10:294-298.
50. Chinnasamy D, et al. Local delivery of interleukin-12 using T cells targeting VEGF receptor-2 eradicates multiple vascularized tumors in mice. Clin Cancer Res 2012;18:1672-1683.
51. Jaalouk DE, Lejeune L, Couture C, Galipeau J. A self-inactivating retrovector incorporating the IL-2 promoter for activation-induced transgene expression in genetically engineered T-cells. Virol J 2006;3:97.
52. Gattinoni L, et al. Removal of homeostatic cytokine sinks by lymphodepletion enhances the efficacy of adoptively transferred tumor-specific CD8+ T cells. J Exp Med 2005;202:907-912.
53. Schurich A, et al. The third signal cytokine IL-12 rescues the anti-viral function of exhausted HBV-specific CD8 T cells. PLoS Pathog 2013;3:e1003208.
54. Durrant DM, Metzger DW. IL-12 can alleviate Th17-mediated allergic lung inflammation through induction of pulmonary IL-10 expression. Mucosal Immunol 2010;3:301-311.
55. Hunter CA. New IL-12-family members: IL-23 and IL-27, cytokines with divergent functions. Nat Rev Immunol 2005;5:521-531.
56. Oppmann B, et al. Novel p19 protein engages IL-12p40 to form a cytokine, IL-23, with biological activities similar as well as distinct from IL-12. Immunity 2000;13:715-725.
57. Langowski JL, et al. IL-23 promotes tumor incidence and growth. Nature 2006;442:461-465.
58. Ju DW, et al. Interleukin-18 gene transfer increases antitumor effects of suicide gene therapy through efficient induction of antitumor immunity. Gene Ther 2000;7:1672-1679.
59. Munder M, Mallo M, Eichmann K, Modolell M. Murine macrophages secrete interferon gamma upon combined stimulation with interleukin (IL)-12 and IL-18: a novel pathway of autocrine macrophage activation. J Exp Med 1998;187:2103-2108.
60. Wagner HJ, et al. Expansion of EBV latent membrane protein 2a specific cytotoxic T cells for the adoptive immunotherapy of EBV latency type 2 malignancies: influence of recombinant IL12 and IL15. Cytotherapy 2003;5:231-240.
61. Egilmez NK, Harden JL, Virtuoso LP, Schwendener RA, Kilinc MO. Nitric oxide short-circuits interleukin-12-mediated tumor regression. Cancer Immunol Immunother 2011;60:839-845.
62. Rosenberg SA. Cell Therapy for Metastatic Melanoma Using CD8 Enriched Tumor Infiltrating Lymphocytes, 2011. Available from www.ClinicalTrials.gov; NCT01236573.