513
Views
5
CrossRef citations to date
0
Altmetric
Review

Reprogramming T-cells for adoptive immunotherapy of ovarian cancer

, , , &
Pages 359-367 | Received 13 Sep 2017, Accepted 05 Jan 2018, Published online: 10 Jan 2018

References

  • Siegel RL, Miller KD, Jemal A. Cancer statistics, 2016. CA Cancer J Clin. 2016 Jan-Feb;66(1):7–30. PubMed PMID: 26742998; eng. DOI:10.3322/caac.21332
  • Harter P, Sehouli J, Reuss A, et al. Prospective validation study of a predictive score for operability of recurrent ovarian cancer: the Multicenter Intergroup Study DESKTOP II. A project of the AGO Kommission OVAR, AGO Study Group, NOGGO, AGO-Austria, and MITO. Int J Gynecol Cancer. 2011 Feb;21(2):289–295. PubMed PMID: 21270612; eng.
  • Aghajanian C, Blank SV, Goff BA, et al. OCEANS: a randomized, double-blind, placebo-controlled phase III trial of chemotherapy with or without bevacizumab in patients with platinum-sensitive recurrent epithelial ovarian, primary peritoneal, or fallopian tube cancer. J Clin Oncol. 2012 Jun;30(17):2039–2045. PubMed PMID: 22529265; PubMed Central PMCID: PMCPMC3646321. eng.
  • Pujade-Lauraine E, Hilpert F, Weber B, et al. Bevacizumab combined with chemotherapy for platinum-resistant recurrent ovarian cancer: the AURELIA open-label randomized phase III trial. J Clin Oncol. 2014 May;32(13):1302–1308. PubMed PMID: 24637997; eng.
  • Ledermann J, Harter P, Gourley C, et al. Olaparib maintenance therapy in patients with platinum-sensitive relapsed serous ovarian cancer: a preplanned retrospective analysis of outcomes by BRCA status in a randomised phase 2 trial. Lancet Oncol. 2014 Jul;15(8):852–861. PubMed PMID: 24882434; eng.
  • Mirza MR, Monk BJ, Herrstedt J, et al. Niraparib maintenance therapy in platinum-sensitive, recurrent ovarian cancer. N Engl J Med. 2016 12;375(22):2154–2164. PubMed PMID: 27717299; eng.
  • Pujade-Lauraine E, Ledermann JA, Selle F, et al. Olaparib tablets as maintenance therapy in patients with platinum-sensitive, relapsed ovarian cancer and a BRCA1/2 mutation (SOLO2/ENGOT-Ov21): a double-blind, randomised, placebo-controlled, phase 3 trial. Lancet Oncol. 2017 Jul. PubMed PMID: 28754483; eng. DOI:10.1016/S1470-2045(17)30469-2
  • Swisher EM, Lin KK, Oza AM, et al. Rucaparib in relapsed, platinum-sensitive high-grade ovarian carcinoma (ARIEL2 Part 1): an international, multicentre, open-label, phase 2 trial. Lancet Oncol. 2017 Jan;18(1):75–87. PubMed PMID: 27908594; eng.
  • Koebel CM, Vermi W, Swann JB, et al. Adaptive immunity maintains occult cancer in an equilibrium state. Nature. 2007 Dec;450(7171):903–907. PubMed PMID: 18026089; eng.
  • Freeman GJ, Long AJ, Iwai Y, et al. Engagement of the PD-1 immunoinhibitory receptor by a novel B7 family member leads to negative regulation of lymphocyte activation. J Exp Med. 2000 Oct;192(7):1027–1034. PubMed PMID: 11015443; PubMed Central PMCID: PMCPMC2193311. eng.
  • Francisco LM, Salinas VH, Brown KE, et al. PD-L1 regulates the development, maintenance, and function of induced regulatory T cells. J Exp Med. 2009 Dec;206(13):3015–3029. PubMed PMID: 20008522; PubMed Central PMCID: PMCPMC2806460. eng.
  • Worzfeld T, Pogge von Strandmann E, Huber M, et al. The unique molecular and cellular microenvironment of ovarian cancer. Front Oncol. 2017;7:24. PubMed PMID: 28275576; PubMed Central PMCID: PMCPMC5319992. eng. DOI:10.3389/fonc.2017.00024
  • Hu YL, Tee MK, Goetzl EJ, et al. Lysophosphatidic acid induction of vascular endothelial growth factor expression in human ovarian cancer cells. J Natl Cancer Inst. 2001 May;93(10):762–768. PubMed PMID: 11353786; eng.
  • Mills GB, May C, Hill M, et al. Ascitic fluid from human ovarian cancer patients contains growth factors necessary for intraperitoneal growth of human ovarian adenocarcinoma cells. J Clin Invest. 1990 Sep;86(3):851–855. PubMed PMID: 2394835; PubMed Central PMCID: PMCPMC296802. eng.
  • Zhang L, Conejo-Garcia JR, Katsaros D, et al. Intratumoral T cells, recurrence, and survival in epithelial ovarian cancer. N Engl J Med. 2003 Jan;348(3):203–213. PubMed PMID: 12529460; eng.
  • Matsuzaki J, Gnjatic S, Mhawech-Fauceglia P, et al. Tumor-infiltrating NY-ESO-1-specific CD8+ T cells are negatively regulated by LAG-3 and PD-1 in human ovarian cancer. Proc Natl Acad Sci USA. 2010 Apr;107(17):7875–7880. PubMed PMID: 20385810; PubMed Central PMCID: PMCPMC2867907. eng.
  • Huang RY, Eppolito C, Lele S, et al. LAG3 and PD1 co-inhibitory molecules collaborate to limit CD8+ T cell signaling and dampen antitumor immunity in a murine ovarian cancer model. Oncotarget. 2015 Sep;29(6):27359–27377. PubMed PMID: 26318293; PubMed Central PMCID: PMCPMC4694995. eng. DOI:10.18632/oncotarget.4751
  • McAlpine JN, Porter H, Köbel M, et al. BRCA1 and BRCA2 mutations correlate with TP53 abnormalities and presence of immune cell infiltrates in ovarian high-grade serous carcinoma. Mod Pathol. 2012 May;25(5):740–750. PubMed PMID: 22282309; eng.
  • Strickland KC, Howitt BE, Shukla SA, et al. Association and prognostic significance of BRCA1/2-mutation status with neoantigen load, number of tumor-infiltrating lymphocytes and expression of PD-1/PD-L1 in high grade serous ovarian cancer. Oncotarget. 2016 Mar;7(12):13587–13598. PubMed PMID: 26871470; eng. DOI:10.18632/oncotarget.7277
  • Ribas A, Hamid O, Daud A, et al. Association of pembrolizumab with tumor response and survival among patients with advanced melanoma. Jama. 2016 Apr;315(15):1600–1609. PubMed PMID: 27092830; eng.
  • Robert C, Schachter J, Long GV, et al. Pembrolizumab versus ipilimumab in advanced melanoma. N Engl J Med. 2015 Jun;372(26):2521–2532. PubMed PMID: 25891173; eng.
  • Ribas A, Puzanov I, Dummer R, et al. Pembrolizumab versus investigator-choice chemotherapy for ipilimumab-refractory melanoma (KEYNOTE-002): a randomised, controlled, phase 2 trial. Lancet Oncol. 2015 Aug;16(8):908–918. PubMed PMID: 26115796; eng.
  • Robert C, Long GV, Brady B, et al. Nivolumab in previously untreated melanoma without BRAF mutation. N Engl J Med. 2015 Jan;372(4):320–330. PubMed PMID: 25399552; eng.
  • Weber JS, D’Angelo SP, Minor D, et al. Nivolumab versus chemotherapy in patients with advanced melanoma who progressed after anti-CTLA-4 treatment (CheckMate 037): a randomised, controlled, open-label, phase 3 trial. Lancet Oncol. 2015 Apr;16(4):375–384. PubMed PMID: 25795410; eng.
  • Armand P, Shipp MA, Ribrag V, et al. Programmed death-1 blockade with pembrolizumab in patients with classical Hodgkin lymphoma after brentuximab vedotin failure. J Clin Oncol. 2016 Jun;34:3733–3739. PubMed PMID: 27354476; eng.
  • Ansell SM, Lesokhin AM, Borrello I, et al. PD-1 blockade with nivolumab in relapsed or refractory Hodgkin’s lymphoma. N Engl J Med. 2015 Jan;372(4):311–319. PubMed PMID: 25482239; PubMed Central PMCID: PMCPMC4348009. eng.
  • Brahmer J, Reckamp KL, Baas P, et al. Nivolumab versus docetaxel in advanced squamous-cell non-small-cell lung cancer. N Engl J Med. 2015 Jul;373(2):123–135. PubMed PMID: 26028407; PubMed Central PMCID: PMCPMC4681400. eng.
  • Reck M, Rodríguez-Abreu D, Robinson AG, et al. Pembrolizumab versus chemotherapy for PD-L1-positive non-small-cell lung cancer. N Engl J Med. 2016 11;375(19):1823–1833. PubMed PMID: 27718847; eng.
  • Balar AV, Galsky MD, Rosenberg JE, et al. Atezolizumab as first-line treatment in cisplatin-ineligible patients with locally advanced and metastatic urothelial carcinoma: a single-arm, multicentre, phase 2 trial. Lancet. 2017 01;389(10064):67–76. PubMed PMID: 27939400; PubMed Central PMCID: PMCPMC5568632. eng.
  • Rosenberg JE, Hoffman-Censits J, Powles T, et al. Atezolizumab in patients with locally advanced and metastatic urothelial carcinoma who have progressed following treatment with platinum-based chemotherapy: a single-arm, multicentre, phase 2 trial. Lancet. 2016 May;387(10031):1909–1920. PubMed PMID: 26952546; eng.
  • Motzer RJ, Hutson TE, Ren M, et al. Independent assessment of lenvatinib plus everolimus in patients with metastatic renal cell carcinoma. Lancet Oncol. 2016 Jan;17(1):e4–5. PubMed PMID: 26758760; eng.
  • Disis ML, Patel MR, Pant S, et al. Avelumab (MSB0010718C; anti-PD-L1) in patients with recurrent/refractory ovarian cancer from the JAVELIN Solid Tumor phase Ib trial: safety and clinical activity. J Clin Oncol. 2016;34:(suppl; abstr 5533).
  • Varga A, Piha-Paul SA, Ott PA, et al. Antitumor activity and safety of pembrolizumab in patients (pts) with PD-L1 positive advanced ovarian cancer: interim results from a phase Ib study. J Clin Oncol. 2015;33(suppl; abstr 5510).
  • Hamanishi J, Mandai M, Ikeda T, et al. Safety and antitumor activity of anti-PD-1 antibody, nivolumab, in patients with platinum-resistant ovarian cancer. J Clin Oncol. 2015 Dec;33(34):4015–4022. PubMed PMID: 26351349; eng. DOI:10.1200/JCO.2015.62.3397
  • Mittica G, Genta S, Aglietta M, et al. Immune checkpoint inhibitors: a new opportunity in the treatment of ovarian cancer? Int J Mol Sci. 2016 Jul;17(7). PubMed PMID: 27447625; PubMed Central PMCID: PMCPMC4964540. eng. DOI:10.3390/ijms17071169
  • Rosenberg SA, Dudley ME. Adoptive cell therapy for the treatment of patients with metastatic melanoma. Curr Opin Immunol. 2009 Apr;21(2):233–240. PubMed PMID: 19304471; PubMed Central PMCID: PMCPMC3459355. eng. DOI:10.1016/j.coi.2009.03.002
  • Mittica G, Capellero S, Genta S, et al. Adoptive immunotherapy against ovarian cancer. J Ovarian Res. 2016 May;9(1):30. PubMed PMID: 27188274; PubMed Central PMCID: PMCPMC4869278. eng.
  • Chmielewski M, Hombach AA, Abken H. Antigen-specific T-cell activation independently of the MHC: chimeric antigen receptor-redirected T cells. Front Immunol. 2013;4:371. PubMed PMID: 24273543; PubMed Central PMCID: PMCPMC3822734. eng. DOI:10.3389/fimmu.2013.00371
  • Harris DT, Kranz DM. Adoptive T cell therapies: a comparison of T cell receptors and chimeric antigen receptors. Trends Pharmacol Sci. 2016 Mar;37(3):220–230. PubMed PMID: 26705086; PubMed Central PMCID: PMCPMC4764454. eng. DOI:10.1016/j.tips.2015.11.004
  • Dotti G, Gottschalk S, Savoldo B, et al. Design and development of therapies using chimeric antigen receptor-expressing T cells. Immunol Rev. 2014 Jan;257(1):107–126. PubMed PMID: 24329793; PubMed Central PMCID: PMCPMC3874724. eng.
  • Chmielewski M, Abken H. TRUCKs: the fourth generation of CARs. Expert Opin Biol Ther. 2015;15(8):1145–1154. PubMed PMID: 25985798; eng.
  • Di Stasi A, Tey SK, Dotti G, et al. Inducible apoptosis as a safety switch for adoptive cell therapy. N Engl J Med. 2011 Nov;365(18):1673–1683. PubMed PMID: 22047558; PubMed Central PMCID: PMCPMC3236370. eng. DOI:10.1056/NEJMoa1106152
  • Ciceri F, Bonini C, Stanghellini MT, et al. Infusion of suicide-gene-engineered donor lymphocytes after family haploidentical haemopoietic stem-cell transplantation for leukaemia (the TK007 trial): a non-randomised phase I-II study. Lancet Oncol. 2009 May;10(5):489–500. PubMed PMID: 19345145; eng.
  • Gargett T, Brown MP. The inducible caspase-9 suicide gene system as a “safety switch” to limit on-target, off-tumor toxicities of chimeric antigen receptor T cells. Front Pharmacol. 2014;5:235. PubMed PMID: 25389405; PubMed Central PMCID: PMCPMC4211380. eng. DOI:10.3389/fphar.2014.00235
  • Barrett DM, Liu X, Jiang S, et al. Regimen-specific effects of RNA-modified chimeric antigen receptor T cells in mice with advanced leukemia. Hum Gene Ther. 2013 Aug;24(8):717–727. PubMed PMID: 23883116; PubMed Central PMCID: PMCPMC3746289. eng.
  • Schutsky K, Song DG, Lynn R, et al. Rigorous optimization and validation of potent RNA CAR T cell therapy for the treatment of common epithelial cancers expressing folate receptor. Oncotarget. 2015 Oct;6(30):28911–28928. PubMed PMID: 26359629; PubMed Central PMCID: PMCPMC4745700. eng.
  • Beatty GL, Haas AR, Maus MV, et al. Mesothelin-specific chimeric antigen receptor mRNA-engineered T cells induce anti-tumor activity in solid malignancies. Cancer Immunol Res. 2014 Feb;2(2):112–120. PubMed PMID: 24579088; PubMed Central PMCID: PMCPMC3932715. eng.
  • Porter DL, Levine BL, Kalos M, et al. Chimeric antigen receptor-modified T cells in chronic lymphoid leukemia. N Engl J Med. 2011 Aug;365(8):725–733. PubMed PMID: 21830940; PubMed Central PMCID: PMCPMC3387277. eng.
  • Grupp SA, Kalos M, Barrett D, et al. Chimeric antigen receptor-modified T cells for acute lymphoid leukemia. N Engl J Med. 2013 Apr;368(16):1509–1518. PubMed PMID: 23527958; PubMed Central PMCID: PMCPMC4058440. eng.
  • Kalos M, Levine BL, Porter DL, 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 Aug;3(95):95ra73. PubMed PMID: 21832238; PubMed Central PMCID: PMCPMC3393096. eng.
  • Maude SL, Frey N, Shaw PA, et al. Chimeric antigen receptor T cells for sustained remissions in leukemia. N Engl J Med. 2014 Oct;16(371):1507–1517. PubMed PMID: 25317870; PubMed Central PMCID: PMCPMC4267531. eng. DOI:10.1056/NEJMoa1407222
  • Brentjens RJ, Rivière I, Park JH, 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 Nov;118(18):4817–4828. PubMed PMID: 21849486; PubMed Central PMCID: PMCPMC3208293. eng.
  • Porter DL, Hwang WT, Frey NV, et al. Chimeric antigen receptor T cells persist and induce sustained remissions in relapsed refractory chronic lymphocytic leukemia. Sci Transl Med. 2015 Sep;7(303):303ra139. PubMed PMID: 26333935; eng.
  • Curran K, Riviere I, Silverman L, et al. Multi-center clinical trial of CAR Tcells in pediatric/young adult patients with relapsed B-cell ALL. Blood. 2015;126(suppl 23, ASH abstract 2533).
  • Lee DW, Kochenderfer JN, Stetler-Stevenson M, et al. T cells expressing CD19 chimeric antigen receptors for acute lymphoblastic leukaemia in children and young adults: a phase 1 dose-escalation trial. Lancet. 2015 Feb;385(9967):517–528. PubMed PMID: 25319501; eng.
  • Li W, Song X, Jin Y, et al. CARTs for solid tumors: feasible or infeasible? Oncol Res Treat. 2017;40(9):540–546.
  • Yazdanifar M, Zhou R, Mukherjee P. Emerging immunotherapeutics in adenocarcinomas: a focus on CAR-T cells. Curr Trends Immunol. 2016;17:95–115. PubMed PMID: 28659689; PubMed Central PMCID: PMCPMC5484157. eng.
  • Louis CU, Savoldo B, Dotti G, et al. Antitumor activity and long-term fate of chimeric antigen receptor-positive T cells in patients with neuroblastoma. Blood. 2011 Dec;118(23):6050–6056. PubMed PMID: 21984804; PubMed Central PMCID: PMCPMC3234664. eng.
  • Ahmed N, Brawley VS, Hegde M, et al. Human epidermal growth factor receptor 2 (HER2) -specific chimeric antigen receptor-modified T cells for the immunotherapy of HER2-positive sarcoma. J Clin Oncol. 2015 May;33(15):1688–1696. PubMed PMID: 25800760; PubMed Central PMCID: PMCPMC4429176. eng.
  • Feng K, Guo Y, Dai H, et al. Chimeric antigen receptor-modified T cells for the immunotherapy of patients with EGFR-expressing advanced relapsed/refractory non-small cell lung cancer. Sci China Life Sci. 2016 May;59(5):468–479. PubMed PMID: 26968708; eng.
  • Katz SC, Burga RA, McCormack E, et al. Phase I hepatic immunotherapy for metastases study of intra-arterial chimeric antigen receptor-modified T-cell therapy for CEA+ liver metastases. Clin Cancer Res. 2015 Jul;21(14):3149–3159. PubMed PMID: 25850950; PubMed Central PMCID: PMCPMC4506253. eng.
  • Bonifant C, Jackson H, Brentjens RJ, et al. Toxicity and management in CAR T-cell therapy. Mol Ther Oncolytics. 2016 Apr 20;3:16011.
  • Tanyi JL, Stashwick C, Plesa G, et al. Possible compartmental cytokine release syndrome in a patient with recurrent ovarian cancer after treatment with mesothelin-targeted CAR-T cells. J Immunother. 2017 Apr;40(3):104–107. PubMed PMID: 28234665; eng.
  • Brentjens R, Yeh R, Bernal Y, et al. Treatment of chronic lymphocytic leukemia with genetically targeted autologous T cells: case report of an unforeseen adverse event in a phase I clinical trial. Mol Ther. 2010 Apr;18(4):666–668.
  • Morgan RA, Yang JC, Kitano M, et al. Case report of a serious adverse event following the administration of T cells transduced with a chimeric antigen receptor recognizing ERBB2. Mol Ther. 2010 Apr;18(4):843–851. PubMed PMID: 20179677; PubMed Central PMCID: PMCPMC2862534. eng.
  • Coney LR, Tomassetti A, Carayannopoulos L, et al. Cloning of a tumor-associated antigen: mOv18 and MOv19 antibodies recognize a folate-binding protein. Cancer Res. 1991 Nov;51(22):6125–6132. PubMed PMID: 1840502; eng.
  • Verri E, Guglielmini P, Puntoni M, et al. HER2/neu oncoprotein overexpression in epithelial ovarian cancer: evaluation of its prevalence and prognostic significance. Clinical study. Oncology. 2005;68(2–3):154–161. PubMed PMID: 16020953; eng. DOI:10.1159/000086958
  • Chang K, Pastan I. Molecular cloning of mesothelin, a differentiation antigen present on mesothelium, mesotheliomas, and ovarian cancers. Proc Natl Acad Sci USA. 1996 Jan;93(1):136–140. PubMed PMID: 8552591; PubMed Central PMCID: PMCPMC40193. eng.
  • Kloudová K, Hromádková H, Partlová S, et al. Expression of tumor antigens on primary ovarian cancer cells compared to established ovarian cancer cell lines. Oncotarget. 2016 Jul;7(29):46120–46126. PubMed PMID: 27323861; PubMed Central PMCID: PMCPMC5216785. eng.
  • Patriarca C, Macchi RM, Marschner AK, et al. Epithelial cell adhesion molecule expression (CD326) in cancer: a short review. Cancer Treat Rev. 2012 Feb;38(1):68–75. PubMed PMID: 21576002; eng.
  • Chekmasova AA, Rao TD, Nikhamin Y, et al. Successful eradication of established peritoneal ovarian tumors in SCID-Beige mice following adoptive transfer of T cells genetically targeted to the MUC16 antigen. Clin Cancer Res. 2010 Jul;16(14):3594–3606. PubMed PMID: 20628030; PubMed Central PMCID: PMCPMC2907178. eng. DOI:10.1158/1078-0432.CCR-10-0192
  • Hong H, Brown CE, Ostberg JR, et al. L1 cell adhesion molecule-specific chimeric antigen receptor-redirected human T cells exhibit specific and efficient antitumor activity against human ovarian cancer in mice. PLoS One. 2016;11(1):e0146885. PubMed PMID: 26761817; PubMed Central PMCID: PMCPMC4711972. eng.
  • Ang WX, Li Z, Chi Z, et al. Intraperitoneal immunotherapy with T cells stably and transiently expressing anti-EpCAM CAR in xenograft models of peritoneal carcinomatosis. Oncotarget. 2017 Feb;8(8):13545–13559. PubMed PMID: 28088790; PubMed Central PMCID: PMCPMC5355119. eng.
  • Song DG, Ye Q, Santoro S, et al. Chimeric NKG2D CAR-expressing T cell-mediated attack of human ovarian cancer is enhanced by histone deacetylase inhibition. Hum Gene Ther. 2013 Mar;24(3):295–305. PubMed PMID: 23297870; PubMed Central PMCID: PMCPMC3609608. eng.
  • Kershaw MH, Westwood JA, Parker LL, et al. A phase I study on adoptive immunotherapy using gene-modified T cells for ovarian cancer. Clin Cancer Res. 2006 Oct;12(20 Pt 1):6106–6115. PubMed PMID: 17062687; PubMed Central PMCID: PMCPMC2154351. eng. DOI:10.1158/1078-0432.CCR-06-1183
  • Tanyi JL, Haas AR, Beatty GL, et al. Anti-mesothelin chimeric antigen receptor T cells in patients with epithelial ovarian cancer. J Clin Oncol. 2016;34(suppl; abstr 5511).
  • Checkmasova AA, Sandadi S, Spriggs DR. Effect of modulation of the hostile tumor microenvironment through adoptive transfer of IL-12 expressing MUC 16 targeted T cells on ovarian tumors in vivo. J Clin Oncol. 2012;30(suppl; abstr 2586).
  • Yeku OO, Purdon T, Spriggs DR, et al. Chimeric antigen receptor (CAR) T cells genetically engineered to deliver IL-12 to the tumor microenvironment in ovarian cancer. J Clin Oncol. 2017;35(Suppl 7s; abstr 141).
  • Xu X, Jin Q, Sun Y. The basics of CAR T design and challenges in immunotherapy of solid tumors - Ovarian cancer as a model. Hum Vaccin Immunother. 2017 Jul 3;13(7):1548–1555.
  • Tewari D, Java JJ, Salani R, et al. Long-term survival advantage and prognostic factors associated with intraperitoneal chemotherapy treatment in advanced ovarian cancer: a gynecologic oncology group study. J Clin Oncol. 2015 May;33(13):1460–1466. PubMed PMID: 25800756; PubMed Central PMCID: PMCPMC4404424. eng.
  • [ cited 2017 Dec 21]. Available from: http://www.onclive.com/web-exclusives/novartis-sets-a-price-of-475000-for-car-tcell-therapy
  • Suarez ER, Chang DK, Sun J, et al. Chimeric antigen receptor T cells secreting anti-PD-L1 antibodies more effectively regress renal cell carcinoma in a humanized mouse model. Oncotarget. 2016 Jun;7(23):34341–34355. PubMed PMID: 27145284; PubMed Central PMCID: PMCPMC5085160. eng.
  • Xia AL, Wang XC, Lu YJ, et al. Chimeric-antigen receptor T (CAR-T) cell therapy for solid tumors: challenges and opportunities. Oncotarget. 2017 Oct;8(52):90521–90531. PubMed PMID: 29163850; PubMed Central PMCID: PMCPMC5685771. eng.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.