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Published in: BMC Cancer 1/2019

Open Access 01-12-2019 | Lymphoma | Review

Challenges of driving CD30-directed CAR-T cells to the clinic

Authors: Natalie S. Grover, Barbara Savoldo

Published in: BMC Cancer | Issue 1/2019

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Abstract

Chimeric antigen receptor T (CAR-T) cells are a promising new treatment for patients with relapsed or refractory hematologic malignancies, including lymphoma. Given the success of CAR-T cells directed against CD19, new targets are being developed and tested, since not all lymphomas express CD19. CD30 is promising target as it is universally expressed in virtually all classical Hodgkin lymphomas, anaplastic large cell lymphomas, and in a proportion of other lymphoma types, including cutaneous T cell lymphomas and diffuse large B cell lymphomas. Preclinical studies with CD30-directed CAR-T cells support the feasibility of this approach. Recently, two clinical trials of CD30-directed CAR-T cells in relapsed/refractory CD30+ lymphomas, including Hodgkin lymphoma, have been reported with minimal toxicities noted and preliminary efficacy seen in a proportion of patients. However, improving the persistence and expansion of CAR-T cells is key to further enhancing the efficacy of this treatment approach. Future directions include optimizing the lymphodepletion regimen, enhancing migration to the tumor site, and combination with other immune regulators. Several ongoing and upcoming clinical trials of CD30-directed CAR-T cells are expected to further enhance this approach to treat patients with relapsed and refractory CD30+ lymphomas.
Literature
1.
go back to reference 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 or zeta subunits of the immunoglobulin and T-cell receptors. Proc Natl Acad Sci U S A. 1993;90(2):720–4.PubMedPubMedCentral 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 or zeta subunits of the immunoglobulin and T-cell receptors. Proc Natl Acad Sci U S A. 1993;90(2):720–4.PubMedPubMedCentral
2.
go back to reference Sadelain M, Brentjens R, Riviere I. The basic principles of chimeric antigen receptor design. Cancer Discov. 2013;3(4):388–98.PubMedPubMedCentral Sadelain M, Brentjens R, Riviere I. The basic principles of chimeric antigen receptor design. Cancer Discov. 2013;3(4):388–98.PubMedPubMedCentral
3.
go back to reference Scheuermann RH, Racila E. CD19 antigen in leukemia and lymphoma diagnosis and immunotherapy. Leuk Lymphoma. 1995;18(5–6):385–97.PubMed Scheuermann RH, Racila E. CD19 antigen in leukemia and lymphoma diagnosis and immunotherapy. Leuk Lymphoma. 1995;18(5–6):385–97.PubMed
4.
go back to reference Neelapu SS, Locke FL, Bartlett NL, Lekakis LJ, Miklos DB, Jacobson CA, Braunschweig I, Oluwole OO, Siddiqi T, Lin Y, et al. Axicabtagene Ciloleucel CAR T-cell therapy in refractory large B-cell lymphoma. N Engl J Med. 2017;377(26):2531–44.PubMedPubMedCentral Neelapu SS, Locke FL, Bartlett NL, Lekakis LJ, Miklos DB, Jacobson CA, Braunschweig I, Oluwole OO, Siddiqi T, Lin Y, et al. Axicabtagene Ciloleucel CAR T-cell therapy in refractory large B-cell lymphoma. N Engl J Med. 2017;377(26):2531–44.PubMedPubMedCentral
5.
go back to reference Schuster SJ, Svoboda J, Chong EA, Nasta SD, Mato AR, Anak Ö, Brogdon JL, Pruteanu-Malinici I, Bhoj V, Landsburg D, et al. Chimeric antigen receptor T cells in refractory B-cell lymphomas. N Engl J Med. 2017;377(26):2545–54.PubMedPubMedCentral Schuster SJ, Svoboda J, Chong EA, Nasta SD, Mato AR, Anak Ö, Brogdon JL, Pruteanu-Malinici I, Bhoj V, Landsburg D, et al. Chimeric antigen receptor T cells in refractory B-cell lymphomas. N Engl J Med. 2017;377(26):2545–54.PubMedPubMedCentral
6.
go back to reference Glimelius I, Ekberg S, Jerkeman M, Chang ET, Bjorkholm M, Andersson TM, Smedby KE, Eloranta S. Long-term survival in young and middle-aged Hodgkin lymphoma patients in Sweden 1992-2009-trends in cure proportions by clinical characteristics. Am J Hematol. 2015;90(12):1128–34.PubMed Glimelius I, Ekberg S, Jerkeman M, Chang ET, Bjorkholm M, Andersson TM, Smedby KE, Eloranta S. Long-term survival in young and middle-aged Hodgkin lymphoma patients in Sweden 1992-2009-trends in cure proportions by clinical characteristics. Am J Hematol. 2015;90(12):1128–34.PubMed
7.
go back to reference Schmitz N, Pfistner B, Sextro M, Sieber M, Carella AM, Haenel M, Boissevain F, Zschaber R, Muller P, Kirchner H, et al. Aggressive conventional chemotherapy compared with high-dose chemotherapy with autologous haemopoietic stem-cell transplantation for relapsed chemosensitive Hodgkin's disease: a randomised trial. Lancet (London, England). 2002;359(9323):2065–71. Schmitz N, Pfistner B, Sextro M, Sieber M, Carella AM, Haenel M, Boissevain F, Zschaber R, Muller P, Kirchner H, et al. Aggressive conventional chemotherapy compared with high-dose chemotherapy with autologous haemopoietic stem-cell transplantation for relapsed chemosensitive Hodgkin's disease: a randomised trial. Lancet (London, England). 2002;359(9323):2065–71.
8.
go back to reference Sarina B, Castagna L, Farina L, Patriarca F, Benedetti F, Carella AM, Falda M, Guidi S, Ciceri F, Bonini A, et al. Allogeneic transplantation improves the overall and progression-free survival of Hodgkin lymphoma patients relapsing after autologous transplantation: a retrospective study based on the time of HLA typing and donor availability. Blood. 2010;115(18):3671–7.PubMed Sarina B, Castagna L, Farina L, Patriarca F, Benedetti F, Carella AM, Falda M, Guidi S, Ciceri F, Bonini A, et al. Allogeneic transplantation improves the overall and progression-free survival of Hodgkin lymphoma patients relapsing after autologous transplantation: a retrospective study based on the time of HLA typing and donor availability. Blood. 2010;115(18):3671–7.PubMed
9.
go back to reference Hapgood G, Savage KJ. The biology and management of systemic anaplastic large cell lymphoma. Blood. 2015;126(1):17–25.PubMed Hapgood G, Savage KJ. The biology and management of systemic anaplastic large cell lymphoma. Blood. 2015;126(1):17–25.PubMed
10.
go back to reference Dürkop H, Latza U, Hummel M, Eitelbach F, Seed B, Stein H. Molecular cloning and expression of a new member of the nerve growth factor receptor family that is characteristic for Hodgkin's disease. Cell. 1992;68(3):421–7.PubMed Dürkop H, Latza U, Hummel M, Eitelbach F, Seed B, Stein H. Molecular cloning and expression of a new member of the nerve growth factor receptor family that is characteristic for Hodgkin's disease. Cell. 1992;68(3):421–7.PubMed
11.
go back to reference Stein H, Mason DY, Gerdes J, O'Connor N, Wainscoat J, Pallesen G, Gatter K, Falini B, Delsol G, Lemke H, et al. The expression of the Hodgkin's disease associated antigen Ki-1 in reactive and neoplastic lymphoid tissue: evidence that reed-Sternberg cells and histiocytic malignancies are derived from activated lymphoid cells. Blood. 1985;66(4):848–58.PubMed Stein H, Mason DY, Gerdes J, O'Connor N, Wainscoat J, Pallesen G, Gatter K, Falini B, Delsol G, Lemke H, et al. The expression of the Hodgkin's disease associated antigen Ki-1 in reactive and neoplastic lymphoid tissue: evidence that reed-Sternberg cells and histiocytic malignancies are derived from activated lymphoid cells. Blood. 1985;66(4):848–58.PubMed
12.
go back to reference Pierce JM, Mehta A. Diagnostic, prognostic and therapeutic role of CD30 in lymphoma. Expert Rev Hematol. 2017;10(1):29–37.PubMed Pierce JM, Mehta A. Diagnostic, prognostic and therapeutic role of CD30 in lymphoma. Expert Rev Hematol. 2017;10(1):29–37.PubMed
13.
go back to reference Horie R, Watanabe T. CD30: expression and function in health and disease. Semin Immunol. 1998;10(6):457–70.PubMed Horie R, Watanabe T. CD30: expression and function in health and disease. Semin Immunol. 1998;10(6):457–70.PubMed
14.
go back to reference Falini B, Pileri S, Pizzolo G, Durkop H, Flenghi L, Stirpe F, Martelli MF, Stein H. CD30 (Ki-1) molecule: a new cytokine receptor of the tumor necrosis factor receptor superfamily as a tool for diagnosis and immunotherapy. Blood. 1995;85(1):1–14.PubMed Falini B, Pileri S, Pizzolo G, Durkop H, Flenghi L, Stirpe F, Martelli MF, Stein H. CD30 (Ki-1) molecule: a new cytokine receptor of the tumor necrosis factor receptor superfamily as a tool for diagnosis and immunotherapy. Blood. 1995;85(1):1–14.PubMed
15.
go back to reference Hombach A, Heuser C, Sircar R, Tillmann T, Diehl V, Pohl C, Abken H. An anti-CD30 chimeric receptor that mediates CD3-zeta-independent T-cell activation against Hodgkin's lymphoma cells in the presence of soluble CD30. Cancer Res. 1998;58(6):1116–9.PubMed Hombach A, Heuser C, Sircar R, Tillmann T, Diehl V, Pohl C, Abken H. An anti-CD30 chimeric receptor that mediates CD3-zeta-independent T-cell activation against Hodgkin's lymphoma cells in the presence of soluble CD30. Cancer Res. 1998;58(6):1116–9.PubMed
16.
go back to reference Younes A, Gopal AK, Smith SE, Ansell SM, Rosenblatt JD, Savage KJ, Ramchandren R, Bartlett NL, Cheson BD, de Vos S, et al. Results of a pivotal phase II study of brentuximab vedotin for patients with relapsed or refractory Hodgkin's lymphoma. J Clin Oncol. 2012;30(18):2183–9.PubMedPubMedCentral Younes A, Gopal AK, Smith SE, Ansell SM, Rosenblatt JD, Savage KJ, Ramchandren R, Bartlett NL, Cheson BD, de Vos S, et al. Results of a pivotal phase II study of brentuximab vedotin for patients with relapsed or refractory Hodgkin's lymphoma. J Clin Oncol. 2012;30(18):2183–9.PubMedPubMedCentral
17.
go back to reference Pro B, Advani R, Brice P, Bartlett NL, Rosenblatt JD, Illidge T, Matous J, Ramchandren R, Fanale M, Connors JM, et al. Brentuximab vedotin (SGN-35) in patients with relapsed or refractory systemic anaplastic large-cell lymphoma: results of a phase II study. J Clin Oncol. 2012;30(18):2190–6.PubMed Pro B, Advani R, Brice P, Bartlett NL, Rosenblatt JD, Illidge T, Matous J, Ramchandren R, Fanale M, Connors JM, et al. Brentuximab vedotin (SGN-35) in patients with relapsed or refractory systemic anaplastic large-cell lymphoma: results of a phase II study. J Clin Oncol. 2012;30(18):2190–6.PubMed
18.
go back to reference Chen R, Gopal AK, Smith SE, Ansell SM, Rosenblatt JD, Savage KJ, Connors JM, Engert A, Larsen EK, Huebner D, et al. Five-year survival and durability results of brentuximab vedotin in patients with relapsed or refractory Hodgkin lymphoma. Blood. 2016;128(12):1562–6.PubMedPubMedCentral Chen R, Gopal AK, Smith SE, Ansell SM, Rosenblatt JD, Savage KJ, Connors JM, Engert A, Larsen EK, Huebner D, et al. Five-year survival and durability results of brentuximab vedotin in patients with relapsed or refractory Hodgkin lymphoma. Blood. 2016;128(12):1562–6.PubMedPubMedCentral
19.
go back to reference Louis CU, Savoldo B, Dotti G, Pule M, Yvon E, Myers GD, Rossig C, Russell HV, Diouf O, Liu E, et al. Antitumor activity and long-term fate of chimeric antigen receptor-positive T cells in patients with neuroblastoma. Blood. 2011;118(23):6050–6.PubMedPubMedCentral Louis CU, Savoldo B, Dotti G, Pule M, Yvon E, Myers GD, Rossig C, Russell HV, Diouf O, Liu E, et al. Antitumor activity and long-term fate of chimeric antigen receptor-positive T cells in patients with neuroblastoma. Blood. 2011;118(23):6050–6.PubMedPubMedCentral
20.
go back to reference Rooney CM, Smith CA, Ng CY, Loftin SK, Sixbey JW, Gan Y, Srivastava DK, Bowman LC, Krance RA, Brenner MK, et al. Infusion of cytotoxic T cells for the prevention and treatment of Epstein-Barr virus-induced lymphoma in allogeneic transplant recipients. Blood. 1998;92(5):1549–55. Rooney CM, Smith CA, Ng CY, Loftin SK, Sixbey JW, Gan Y, Srivastava DK, Bowman LC, Krance RA, Brenner MK, et al. Infusion of cytotoxic T cells for the prevention and treatment of Epstein-Barr virus-induced lymphoma in allogeneic transplant recipients. Blood. 1998;92(5):1549–55.
21.
go back to reference Savoldo B, Ramos CA, Liu E, Mims MP, Keating MJ, Carrum G, Kamble RT, Bollard CM, Gee AP, Mei Z, et al. CD28 costimulation improves expansion and persistence of chimeric antigen receptor-modified T cells in lymphoma patients. J Clin Invest. 2011;121(5):1822–6.PubMedPubMedCentral Savoldo B, Ramos CA, Liu E, Mims MP, Keating MJ, Carrum G, Kamble RT, Bollard CM, Gee AP, Mei Z, et al. CD28 costimulation improves expansion and persistence of chimeric antigen receptor-modified T cells in lymphoma patients. J Clin Invest. 2011;121(5):1822–6.PubMedPubMedCentral
22.
go back to reference Hombach A, Heuser C, Sircar R, Tillmann T, Diehl V, Pohl C, Abken H. Characterization of a chimeric T-cell receptor with specificity for the Hodgkin's lymphoma-associated CD30 antigen. J Immunother (Hagerstown, Md : 1997). 1999;22(6):473–80. Hombach A, Heuser C, Sircar R, Tillmann T, Diehl V, Pohl C, Abken H. Characterization of a chimeric T-cell receptor with specificity for the Hodgkin's lymphoma-associated CD30 antigen. J Immunother (Hagerstown, Md : 1997). 1999;22(6):473–80.
23.
go back to reference Savoldo B, Rooney CM, Di Stasi A, Abken H, Hombach A, Foster AE, Zhang L, Heslop HE, Brenner MK, Dotti G. Epstein Barr virus specific cytotoxic T lymphocytes expressing the anti-CD30zeta artificial chimeric T-cell receptor for immunotherapy of Hodgkin disease. Blood. 2007;110(7):2620–30.PubMedPubMedCentral Savoldo B, Rooney CM, Di Stasi A, Abken H, Hombach A, Foster AE, Zhang L, Heslop HE, Brenner MK, Dotti G. Epstein Barr virus specific cytotoxic T lymphocytes expressing the anti-CD30zeta artificial chimeric T-cell receptor for immunotherapy of Hodgkin disease. Blood. 2007;110(7):2620–30.PubMedPubMedCentral
24.
go back to reference Dotti G, Gottschalk S, Savoldo B, Brenner MK. Design and development of therapies using chimeric antigen receptor-expressing T cells. Immunol Rev. 2014;257(1):107–26.PubMed Dotti G, Gottschalk S, Savoldo B, Brenner MK. Design and development of therapies using chimeric antigen receptor-expressing T cells. Immunol Rev. 2014;257(1):107–26.PubMed
25.
27.
go back to reference Hombach AA, Gorgens A, Chmielewski M, Murke F, Kimpel J, Giebel B, Abken H. Superior therapeutic index in lymphoma therapy: CD30(+) CD34(+) hematopoietic stem cells resist a chimeric antigen receptor T-cell attack. Mol Ther. 2016;24(8):1423–34.PubMedPubMedCentral Hombach AA, Gorgens A, Chmielewski M, Murke F, Kimpel J, Giebel B, Abken H. Superior therapeutic index in lymphoma therapy: CD30(+) CD34(+) hematopoietic stem cells resist a chimeric antigen receptor T-cell attack. Mol Ther. 2016;24(8):1423–34.PubMedPubMedCentral
28.
go back to reference Beckmann J, Scheitza S, Wernet P, Fischer JC, Giebel B. Asymmetric cell division within the human hematopoietic stem and progenitor cell compartment: identification of asymmetrically segregating proteins. Blood. 2007;109(12):5494–501.PubMed Beckmann J, Scheitza S, Wernet P, Fischer JC, Giebel B. Asymmetric cell division within the human hematopoietic stem and progenitor cell compartment: identification of asymmetrically segregating proteins. Blood. 2007;109(12):5494–501.PubMed
29.
go back to reference Hombach AA, Abken H. Shared target antigens on cancer cells and tissue stem cells: go or no-go for CAR T cells? Expert Rev Clin Immunol. 2017;13(2):151–5.PubMed Hombach AA, Abken H. Shared target antigens on cancer cells and tissue stem cells: go or no-go for CAR T cells? Expert Rev Clin Immunol. 2017;13(2):151–5.PubMed
30.
go back to reference Hong LK, Chen Y, Smith CC, Montgomery SA, Vincent BG, Dotti G, Savoldo B. CD30-redirected chimeric antigen receptor T cells target CD30(+) and CD30(−) embryonal carcinoma via antigen-dependent and Fas/FasL interactions. Cancer Immunol Res. 2018;6(10):1274–87.PubMed Hong LK, Chen Y, Smith CC, Montgomery SA, Vincent BG, Dotti G, Savoldo B. CD30-redirected chimeric antigen receptor T cells target CD30(+) and CD30(−) embryonal carcinoma via antigen-dependent and Fas/FasL interactions. Cancer Immunol Res. 2018;6(10):1274–87.PubMed
31.
go back to reference Wang CM, Wu ZQ, Wang Y, Guo YL, Dai HR, Wang XH, Li X, Zhang YJ, Zhang WY, Chen MX, et al. Autologous T cells expressing CD30 chimeric antigen receptors for relapsed or refractory Hodgkin lymphoma: an open-label phase I trial. Clin Cancer Res. 2017;23(5):1156–66.PubMed Wang CM, Wu ZQ, Wang Y, Guo YL, Dai HR, Wang XH, Li X, Zhang YJ, Zhang WY, Chen MX, et al. Autologous T cells expressing CD30 chimeric antigen receptors for relapsed or refractory Hodgkin lymphoma: an open-label phase I trial. Clin Cancer Res. 2017;23(5):1156–66.PubMed
32.
go back to reference Ramos CA, Ballard B, Zhang H, Dakhova O, Gee AP, Mei Z, Bilgi M, Wu MF, Liu H, Grilley B, et al. Clinical and immunological responses after CD30-specific chimeric antigen receptor-redirected lymphocytes. J Clin Invest. 2017;127(9):3462–71.PubMedPubMedCentral Ramos CA, Ballard B, Zhang H, Dakhova O, Gee AP, Mei Z, Bilgi M, Wu MF, Liu H, Grilley B, et al. Clinical and immunological responses after CD30-specific chimeric antigen receptor-redirected lymphocytes. J Clin Invest. 2017;127(9):3462–71.PubMedPubMedCentral
33.
go back to reference Brentjens RJ, Riviere I, Park JH, Davila ML, Wang X, Stefanski J, Taylor C, Yeh R, Bartido S, Borquez-Ojeda O, et al. Safety and persistence of adoptively transferred autologous CD19-targeted T cells in patients with relapsed or chemotherapy refractory B-cell leukemias. Blood. 2011;118(18):4817–28.PubMedPubMedCentral Brentjens RJ, Riviere I, Park JH, Davila ML, Wang X, Stefanski J, Taylor C, Yeh R, Bartido S, Borquez-Ojeda O, et al. Safety and persistence of adoptively transferred autologous CD19-targeted T cells in patients with relapsed or chemotherapy refractory B-cell leukemias. Blood. 2011;118(18):4817–28.PubMedPubMedCentral
34.
go back to reference Curran KJ, Pegram HJ, Brentjens RJ. Chimeric antigen receptors for T cell immunotherapy: current understanding and future directions. J Gene Med. 2012;14(6):405–15.PubMedPubMedCentral Curran KJ, Pegram HJ, Brentjens RJ. Chimeric antigen receptors for T cell immunotherapy: current understanding and future directions. J Gene Med. 2012;14(6):405–15.PubMedPubMedCentral
35.
go back to reference Haji-Fatahaliha M, Hosseini M, Akbarian A, Sadreddini S, Jadidi-Niaragh F, Yousefi M. CAR-modified T-cell therapy for cancer: an updated review. Artif Cells Nanomed Biotechnol. 2016;44(6):1339–49.PubMed Haji-Fatahaliha M, Hosseini M, Akbarian A, Sadreddini S, Jadidi-Niaragh F, Yousefi M. CAR-modified T-cell therapy for cancer: an updated review. Artif Cells Nanomed Biotechnol. 2016;44(6):1339–49.PubMed
36.
go back to reference Davila ML, Kloss CC, Gunset G, Sadelain M. CD19 CAR-targeted T cells induce long-term remission and B cell aplasia in an immunocompetent mouse model of B cell acute lymphoblastic leukemia. PLoS One. 2013;8(4):e61338.PubMedPubMedCentral Davila ML, Kloss CC, Gunset G, Sadelain M. CD19 CAR-targeted T cells induce long-term remission and B cell aplasia in an immunocompetent mouse model of B cell acute lymphoblastic leukemia. PLoS One. 2013;8(4):e61338.PubMedPubMedCentral
37.
go back to reference Marshall NA, Christie LE, Munro LR, Culligan DJ, Johnston PW, Barker RN, Vickers MA. Immunosuppressive regulatory T cells are abundant in the reactive lymphocytes of Hodgkin lymphoma. Blood. 2004;103(5):1755–62.PubMed Marshall NA, Christie LE, Munro LR, Culligan DJ, Johnston PW, Barker RN, Vickers MA. Immunosuppressive regulatory T cells are abundant in the reactive lymphocytes of Hodgkin lymphoma. Blood. 2004;103(5):1755–62.PubMed
38.
go back to reference Barath S, Aleksza M, Keresztes K, Toth J, Sipka S, Szegedi G, Illes A. Immunoregulatory T cells in the peripheral blood of patients with Hodgkin's lymphoma. Acta Haematol. 2006;116(3):181–5.PubMed Barath S, Aleksza M, Keresztes K, Toth J, Sipka S, Szegedi G, Illes A. Immunoregulatory T cells in the peripheral blood of patients with Hodgkin's lymphoma. Acta Haematol. 2006;116(3):181–5.PubMed
39.
go back to reference Liu Y, Sattarzadeh A, Diepstra A, Visser L, van den Berg A. The microenvironment in classical Hodgkin lymphoma: an actively shaped and essential tumor component. Semin Cancer Biol. 2014;24:15–22.PubMed Liu Y, Sattarzadeh A, Diepstra A, Visser L, van den Berg A. The microenvironment in classical Hodgkin lymphoma: an actively shaped and essential tumor component. Semin Cancer Biol. 2014;24:15–22.PubMed
40.
go back to reference Glimelius I, Diepstra A. Novel treatment concepts in Hodgkin lymphoma. J Intern Med. 2017;281(3):247–60.PubMed Glimelius I, Diepstra A. Novel treatment concepts in Hodgkin lymphoma. J Intern Med. 2017;281(3):247–60.PubMed
41.
go back to reference Gill S, June CH. Going viral: chimeric antigen receptor T-cell therapy for hematological malignancies. Immunol Rev. 2015;263(1):68–89.PubMed Gill S, June CH. Going viral: chimeric antigen receptor T-cell therapy for hematological malignancies. Immunol Rev. 2015;263(1):68–89.PubMed
42.
go back to reference Kochenderfer JN, Dudley ME, Kassim SH, Somerville RP, Carpenter RO, Stetler-Stevenson M, Yang JC, Phan GQ, Hughes MS, Sherry RM, et al. Chemotherapy-refractory diffuse large B-cell lymphoma and indolent B-cell malignancies can be effectively treated with autologous T cells expressing an anti-CD19 chimeric antigen receptor. J Clin Oncol. 2015;33(6):540–9.PubMed Kochenderfer JN, Dudley ME, Kassim SH, Somerville RP, Carpenter RO, Stetler-Stevenson M, Yang JC, Phan GQ, Hughes MS, Sherry RM, et al. Chemotherapy-refractory diffuse large B-cell lymphoma and indolent B-cell malignancies can be effectively treated with autologous T cells expressing an anti-CD19 chimeric antigen receptor. J Clin Oncol. 2015;33(6):540–9.PubMed
43.
go back to reference Klebanoff CA, Khong HT, Antony PA, Palmer DC, Restifo NP. Sinks, suppressors and antigen presenters: how lymphodepletion enhances T cell-mediated tumor immunotherapy. Trends Immunol. 2005;26(2):111–7.PubMedPubMedCentral Klebanoff CA, Khong HT, Antony PA, Palmer DC, Restifo NP. Sinks, suppressors and antigen presenters: how lymphodepletion enhances T cell-mediated tumor immunotherapy. Trends Immunol. 2005;26(2):111–7.PubMedPubMedCentral
44.
go back to reference Di Stasi A, De Angelis B, Rooney CM, Zhang L, Mahendravada A, Foster AE, Heslop HE, Brenner MK, Dotti G, Savoldo B. T lymphocytes coexpressing CCR4 and a chimeric antigen receptor targeting CD30 have improved homing and antitumor activity in a Hodgkin tumor model. Blood. 2009;113(25):6392–402.PubMedPubMedCentral Di Stasi A, De Angelis B, Rooney CM, Zhang L, Mahendravada A, Foster AE, Heslop HE, Brenner MK, Dotti G, Savoldo B. T lymphocytes coexpressing CCR4 and a chimeric antigen receptor targeting CD30 have improved homing and antitumor activity in a Hodgkin tumor model. Blood. 2009;113(25):6392–402.PubMedPubMedCentral
45.
go back to reference van den Berg A, Visser L, Poppema S. High expression of the CC chemokine TARC in reed-Sternberg cells. A possible explanation for the characteristic T-cell infiltratein Hodgkin's lymphoma. Am J Pathol. 1999;154(6):1685–91.PubMedPubMedCentral van den Berg A, Visser L, Poppema S. High expression of the CC chemokine TARC in reed-Sternberg cells. A possible explanation for the characteristic T-cell infiltratein Hodgkin's lymphoma. Am J Pathol. 1999;154(6):1685–91.PubMedPubMedCentral
46.
go back to reference Ishida T, Ishii T, Inagaki A, Yano H, Komatsu H, Iida S, Inagaki H, Ueda R. Specific recruitment of CC chemokine receptor 4-positive regulatory T cells in Hodgkin lymphoma fosters immune privilege. Cancer Res. 2006;66(11):5716–22.PubMed Ishida T, Ishii T, Inagaki A, Yano H, Komatsu H, Iida S, Inagaki H, Ueda R. Specific recruitment of CC chemokine receptor 4-positive regulatory T cells in Hodgkin lymphoma fosters immune privilege. Cancer Res. 2006;66(11):5716–22.PubMed
47.
go back to reference Steidl C, Lee T, Shah SP, Farinha P, Han G, Nayar T, Delaney A, Jones SJ, Iqbal J, Weisenburger DD, et al. Tumor-associated macrophages and survival in classic Hodgkin's lymphoma. N Engl J Med. 2010;362(10):875–85.PubMedPubMedCentral Steidl C, Lee T, Shah SP, Farinha P, Han G, Nayar T, Delaney A, Jones SJ, Iqbal J, Weisenburger DD, et al. Tumor-associated macrophages and survival in classic Hodgkin's lymphoma. N Engl J Med. 2010;362(10):875–85.PubMedPubMedCentral
48.
go back to reference Ansell S, Armand P, Timmerman JM, Shipp MA, Bradley Garelik MB, Zhu L, Lesokhin AM. Nivolumab in patients (pts) with relapsed or refractory classical Hodgkin lymphoma (R/R cHL): clinical outcomes from extended follow-up of a phase 1 study (CA209-039). Blood. 2015;126(23):583. Ansell S, Armand P, Timmerman JM, Shipp MA, Bradley Garelik MB, Zhu L, Lesokhin AM. Nivolumab in patients (pts) with relapsed or refractory classical Hodgkin lymphoma (R/R cHL): clinical outcomes from extended follow-up of a phase 1 study (CA209-039). Blood. 2015;126(23):583.
49.
go back to reference Armand P, Shipp MA, Ribrag V, Michot J-M, Zinzani PL, Kuruvilla J, Zhu Y, Ricart AD, Balakumaran A, Moskowitz CH. Pembrolizumab in patients with classical Hodgkin lymphoma after Brentuximab Vedotin failure: long-term efficacy from the phase 1b Keynote-013 study. In: Am Soc Hematology. 2016. Armand P, Shipp MA, Ribrag V, Michot J-M, Zinzani PL, Kuruvilla J, Zhu Y, Ricart AD, Balakumaran A, Moskowitz CH. Pembrolizumab in patients with classical Hodgkin lymphoma after Brentuximab Vedotin failure: long-term efficacy from the phase 1b Keynote-013 study. In: Am Soc Hematology. 2016.
50.
go back to reference Maude SL, Hucks GE, Seif AE, Talekar MK, Teachey DT, Baniewicz D, Callahan C, Gonzalez V, Nazimuddin F, Gupta M, Frey NV, Porter DL, Levine BL, Melenhorst JJ, Lacey SF, June CH, Grupp SA. The effect of pembrolizumab in combination with CD19-targeted chimeric antigen receptor (CAR) T cells in relapsed acute lymphoblastic leukemia (ALL). Journal of Clinical Oncology; 2017;35(15_suppl);103–103. Maude SL, Hucks GE, Seif AE, Talekar MK, Teachey DT, Baniewicz D, Callahan C, Gonzalez V, Nazimuddin F, Gupta M, Frey NV, Porter DL, Levine BL, Melenhorst JJ, Lacey SF, June CH, Grupp SA. The effect of pembrolizumab in combination with CD19-targeted chimeric antigen receptor (CAR) T cells in relapsed acute lymphoblastic leukemia (ALL). Journal of Clinical Oncology; 2017;35(15_suppl);103–103.
51.
go back to reference Chong EA, Melenhorst JJ, Lacey SF, Ambrose DE, Gonzalez V, Levine BL, June CH, Schuster SJ. PD-1 blockade modulates chimeric antigen receptor (CAR)-modified T cells: refueling the CAR. Blood. 2017;129(8):1039–41.PubMedPubMedCentral Chong EA, Melenhorst JJ, Lacey SF, Ambrose DE, Gonzalez V, Levine BL, June CH, Schuster SJ. PD-1 blockade modulates chimeric antigen receptor (CAR)-modified T cells: refueling the CAR. Blood. 2017;129(8):1039–41.PubMedPubMedCentral
52.
go back to reference Cannarile MA, Weisser M, Jacob W, Jegg A-M, Ries CH, Rüttinger D. Colony-stimulating factor 1 receptor (CSF1R) inhibitors in cancer therapy. J Immunother Cancer. 2017;5(1):53.PubMedPubMedCentral Cannarile MA, Weisser M, Jacob W, Jegg A-M, Ries CH, Rüttinger D. Colony-stimulating factor 1 receptor (CSF1R) inhibitors in cancer therapy. J Immunother Cancer. 2017;5(1):53.PubMedPubMedCentral
53.
go back to reference von Tresckow B, Morschhauser F, Ribrag V, Topp MS, Chien C, Seetharam S, Aquino R, Kotoulek S, de Boer CJ, Engert A. An open-label, multicenter, phase I/II study of JNJ-40346527, a CSF-1R inhibitor, in patients with relapsed or refractory Hodgkin lymphoma. Clin Cancer Res. 2015;21(8):1843–50. von Tresckow B, Morschhauser F, Ribrag V, Topp MS, Chien C, Seetharam S, Aquino R, Kotoulek S, de Boer CJ, Engert A. An open-label, multicenter, phase I/II study of JNJ-40346527, a CSF-1R inhibitor, in patients with relapsed or refractory Hodgkin lymphoma. Clin Cancer Res. 2015;21(8):1843–50.
Metadata
Title
Challenges of driving CD30-directed CAR-T cells to the clinic
Authors
Natalie S. Grover
Barbara Savoldo
Publication date
01-12-2019
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2019
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-019-5415-9

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