中国癌症杂志 ›› 2023, Vol. 33 ›› Issue (7): 707-716.doi: 10.19401/j.cnki.1007-3639.2023.07.009
• 综述 • 上一篇
收稿日期:
2022-08-01
修回日期:
2023-02-15
出版日期:
2023-07-30
发布日期:
2023-08-10
通信作者:
胡康洪(ORCID: 0000-0001-8044-7889),博士,教授。
作者简介:
郑伟涛(ORCID: 0000-0002-0875-7927),博士,高级工程师。
基金资助:
ZHENG Weitao(), LI Hanluo, HU Kanghong(
)
Received:
2022-08-01
Revised:
2023-02-15
Published:
2023-07-30
Online:
2023-08-10
Contact:
HU Kanghong.
文章分享
摘要:
T细胞受体工程T细胞(engineered T cell receptor-T cell,TCR-T)疗法和嵌合抗原受体T细胞(chimeric antigens receptor-T cell,CAR-T)疗法是目前过继性T细胞治疗最有效的两种方式。由于CAR仅能识别肿瘤表面的抗原,在实体瘤治疗中至今未有令人满意的结果。TCR不仅能识别肿瘤表面抗原,同时能识别胞内抗原,因此,TCR-T疗法在治疗实体瘤方面显示出前所未有的前景,成为极具潜力的治疗方式。本综述探讨了TCR-T疗法与CAR-T疗法识别癌症抗原机制的差异及当前TCR-T疗法靶向的临床靶点和不同类型的肿瘤抗原,描述了TCR-T抗肿瘤治疗的临床开发现状,并讨论了临床前评估TCR效价的标准和目前TCR-T治疗的优势、存在的局限性及可能有效的应对措施。最后,我们回顾了TCR-T治疗的现状和当前仍存在的一些挑战,强调靶向肿瘤特异性抗原的重要性,概述了结合检查点阻断治疗和溶瘤病毒等的新抗原特异性TCR-T治疗策略,以期这种联合治疗能够显著改善癌症的免疫治疗效果,并对未来TCR-T治疗根除多发性癌症提供一些思路。
中图分类号:
郑伟涛, 李涵泺, 胡康洪. TCR-T免疫治疗肿瘤:现状、挑战及展望[J]. 中国癌症杂志, 2023, 33(7): 707-716.
ZHENG Weitao, LI Hanluo, HU Kanghong. TCR-T immunotherapy for the treatment of solid tumor: current status, challenges and future prospects[J]. China Oncology, 2023, 33(7): 707-716.
表1
目前各代表性靶点已经进入临床试验阶段的TCR-T治疗方法"
Target | Antigen classification | HLA | Adaptation disease | Clinical phase | Clinical number | Reference |
---|---|---|---|---|---|---|
MART-1 | TAA | A*0201 | Melanoma | Ⅱ | NCT00509288 | [ |
gp100 | TAA | A*0201 | Melanoma | Ⅱ | NCT00509496 | [28] |
CEA | TAA | A*0201 | Metastatic colorectal cancer | Ⅰ/Ⅱ | NCT00923806 | [ |
WT1 | TAA | A*0201 | Acute leukemia/myelodysplastic syndrome | Completed | NCT02550535 | [ |
NY-ESO-1 | TAA | A*0201 | Metastatic melanoma | Ⅱ | NCT00670748 | [ |
MAGE-A3 | TAA | A*01 | Metastatic melanoma | Ⅰ/Ⅱ | NCT01273181 | [ |
MAGE-A4 | TAA | A*02 | Multiple solid tumors | Ⅰ | NCT03132922 | [ |
MAGE-A10 | TAA | A*02 | Multiple solid tumors | Ⅰ | NCT02989064/NCT02592577 | [ |
HPV E6 | TSA | A*0201 | HPV-associated carcinoma | Ⅰ/Ⅱ | NCT02280811 | [ |
HPV E7 | TSA | A*0201 | HPV-associated carcinoma | Ⅰ | NCT02858310 | [ |
p53 | TAA | A*02 | Breast cancer, melanoma, esophagus cancer | Completed | NCT00562640 | [ |
EBV | TSA | A*0201 | Hepatocellular carcinoma | Recruiting | NCT03899415 | [ |
[1] |
MO Z M, DU P X, WANG G P, et al. The multi-purpose tool of tumor immunotherapy: gene-engineered T cells[J]. J Cancer, 2017, 8(9): 1690-1703.
doi: 10.7150/jca.18681 pmid: 28775789 |
[2] |
SCOTT L J. Osimertinib as first-line therapy in advanced NSCLC: a profile of its use[J]. Drugs Ther Perspect, 2018, 34(8): 351-357.
doi: 10.1007/s40267-018-0536-9 |
[3] |
WEBER E W, MAUS M V, MACKALL C L. The emerging landscape of immune cell therapies[J]. Cell, 2020, 181(1): 46-62.
doi: S0092-8674(20)30263-4 pmid: 32243795 |
[4] |
JIANG X T, XU J, LIU M F, et al. Adoptive CD8+ T cell therapy against cancer: challenges and opportunities[J]. Cancer Lett, 2019, 462: 23-32.
doi: 10.1016/j.canlet.2019.07.017 |
[5] |
SALTER A I, RAJAN A, KENNEDY J J, et al. Comparative analysis of TCR and CAR signaling informs CAR designs with superior antigen sensitivity and in vivo function[J]. Sci Signal, 2021, 14(697): eabe2606.
doi: 10.1126/scisignal.abe2606 |
[6] |
XU Y Y, YANG Z Y, HORAN L H, et al. A novel antibody-TCR (AbTCR) platform combines Fab-based antigen recognition with gamma/delta-TCR signaling to facilitate T-cell cytotoxicity with low cytokine release[J]. Cell Discov, 2018, 4: 62.
doi: 10.1038/s41421-018-0066-6 pmid: 30479831 |
[7] |
GARBER K. Driving T-cell immunotherapy to solid tumors[J]. Nat Biotechnol, 2018, 36(3): 215-219.
doi: 10.1038/nbt.4090 pmid: 29509745 |
[8] |
CHAPUIS A G, EGAN D N, BAR M, et al. T cell receptor gene therapy targeting WT1 prevents acute myeloid leukemia relapse post-transplant[J]. Nat Med, 2019, 25(7): 1064-1072.
doi: 10.1038/s41591-019-0472-9 pmid: 31235963 |
[9] |
BLÜTHMANN H, KISIELOW P, UEMATSU Y, et al. T-cell-specific deletion of T-cell receptor transgenes allows functional rearrangement of endogenous alpha- and beta-genes[J]. Nature, 1988, 334(6178): 156-159.
doi: 10.1038/334156a0 |
[10] | BUONAGURO L, TAGLIAMONTE M. Selecting target antigens for cancer vaccine development[J]. Vaccines (Basel), 2020, 8(4): 615. |
[11] | ZHANG J X, WANG L Y. The emerging world of TCR-T cell trials against cancer: a systematic review[J]. Technol Cancer Res Treat, 2019, 18: 1533033819831068. |
[12] |
ZHAO Q J, JIANG Y, XIANG S X, et al. Engineered TCR-T cell immunotherapy in anticancer precision medicine: pros and cons[J]. Front Immunol, 2021, 12: 658753.
doi: 10.3389/fimmu.2021.658753 |
[13] |
HELLMAN L M, FOLEY K C, SINGH N K, et al. Improving T cell receptor on-target specificity via structure-guided design[J]. Mol Ther, 2019, 27(2): 300-313.
doi: S1525-0016(18)30594-X pmid: 30617019 |
[14] |
TAWARA I, KAGEYAMA S, MIYAHARA Y, et al. Safety and persistence of WT1-specific T-cell receptor gene-transduced lymphocytes in patients with AML and MDS[J]. Blood, 2017, 130(18): 1985-1994.
doi: 10.1182/blood-2017-06-791202 pmid: 28860210 |
[15] |
ROBBINS P F, MORGAN R A, FELDMAN S A, et al. Tumor regression in patients with metastatic synovial cell sarcoma and melanoma using genetically engineered lymphocytes reactive with NY-ESO-1[J]. J Clin Oncol, 2011, 29(7): 917-924.
doi: 10.1200/JCO.2010.32.2537 pmid: 21282551 |
[16] |
MORGAN R A, CHINNASAMY N, ABATE-DAGA D, et al. Cancer regression and neurological toxicity following anti-MAGE-A3 TCR gene therapy[J]. J Immunother, 2013, 36(2): 133-151.
doi: 10.1097/CJI.0b013e3182829903 pmid: 23377668 |
[17] | CAMERON B J, GERRY A B, DUKES J, et al. Identification of a Titin-derived HLA-A1-presented peptide as a cross-reactive target for engineered MAGE A3-directed T cells[J]. Sci Transl Med, 2013, 5(197): 197ra103. |
[18] | YE B X, STARY C M, GAO Q P, et al. Genetically modified T-cell-based adoptive immunotherapy in hematological malignancies[J]. J Immunol Res, 2017, 2017: 5210459. |
[19] |
LIM W A, JUNE C H. The principles of engineering immune cells to treat cancer[J]. Cell, 2017, 168(4): 724-740.
doi: S0092-8674(17)30064-8 pmid: 28187291 |
[20] |
MOORE A R, ROSENBERG S C, MCCORMICK F, et al. RAS-targeted therapies: is the undruggable drugged?[J]. Nat Rev Drug Discov, 2020, 19(8): 533-552.
doi: 10.1038/s41573-020-0068-6 pmid: 32528145 |
[21] |
WANG Q J, YU Z Y, GRIFFITH K, et al. Identification of T-cell receptors targeting KRAS-mutated human tumors[J]. Cancer Immunol Res, 2016, 4(3): 204-214.
doi: 10.1158/2326-6066.CIR-15-0188 |
[22] |
MAOZ A, RENNERT G, GRUBER S B. T-cell transfer therapy targeting mutant KRAS[J]. N Engl J Med, 2017, 376(7): e11.
doi: 10.1056/NEJMc1616637 |
[23] |
DESAI J, GAN H, BARROW C, et al. Phase Ⅰ, open-label, dose-escalation/dose-expansion study of lifirafenib (BGB-283), an RAF family kinase inhibitor, in patients with solid tumors[J]. J Clin Oncol, 2020, 38(19): 2140-2150.
doi: 10.1200/JCO.19.02654 |
[24] |
HOOGEVEEN R C, ROBIDOUX M P, SCHWARZ T, et al. Phenotype and function of HBV-specific T cells is determined by the targeted epitope in addition to the stage of infection[J]. Gut, 2019, 68(5): 893-904.
doi: 10.1136/gutjnl-2018-316644 pmid: 30580250 |
[25] |
JIN B Y, CAMPBELL T E, DRAPER L M, et al. Engineered T cells targeting E7 mediate regression of human papillomavirus cancers in a murine model[J]. JCI Insight, 2018, 3(8): e99488.
doi: 10.1172/jci.insight.99488 |
[26] |
NAGARSHETH N B, NORBERG S M, SINKOE A L, et al. TCR-engineered T cells targeting E7 for patients with metastatic HPV-associated epithelial cancers[J]. Nat Med, 2021, 27(3): 419-425.
doi: 10.1038/s41591-020-01225-1 pmid: 33558725 |
[27] |
DRAPER L M, KWONG M L M, GROS A, et al. Targeting of HPV-16+ epithelial cancer cells by TCR gene engineered T cells directed against E6[J]. Clin Cancer Res, 2015, 21(19): 4431-4439.
doi: 10.1158/1078-0432.CCR-14-3341 |
[28] |
JOHNSON L A, MORGAN R A, DUDLEY M E, et al. Gene therapy with human and mouse T-cell receptors mediates cancer regression and targets normal tissues expressing cognate antigen[J]. Blood, 2009, 114(3): 535-546.
doi: 10.1182/blood-2009-03-211714 pmid: 19451549 |
[29] |
PARKHURST M R, YANG J C, LANGAN R C, et al. T cells targeting carcinoembryonic antigen can mediate regression of metastatic colorectal cancer but induce severe transient colitis[J]. Mol Ther, 2011, 19(3): 620-626.
doi: 10.1038/mt.2010.272 pmid: 21157437 |
[30] |
LINETTE G P, STADTMAUER E A, MAUS M V, et al. Cardiovascular toxicity and titin cross-reactivity of affinity-enhanced T cells in myeloma and melanoma[J]. Blood, 2013, 122(6): 863-871.
doi: 10.1182/blood-2013-03-490565 pmid: 23770775 |
[31] | HONG D S, VAN TINE B A, OLSZANSKI A J, et al. Phase Ⅰ dose escalation and expansion trial to assess the safety and efficacy of ADP-A2M4 SPEAR T cells in advanced solid tumors[J]. J Clin Oncol, 2020, 38(15_suppl): 102. |
[32] |
LAM V K, HONG D S, HEYMACH J, et al. Initial safety assessment of MAGE-A10c796 TCR T-cells in two clinical trials[J]. J Clin Oncol, 2018, 36(15_suppl): 3056.
doi: 10.1200/JCO.2018.79.1400 |
[33] |
DORAN S L, STEVANOVIĆ S, ADHIKARY S, et al. T-cell receptor gene therapy for human papillomavirus-associated epithelial cancers: a first-in-human, phase Ⅰ/Ⅱ study[J]. J Clin Oncol, 2019, 37(30): 2759-2768.
doi: 10.1200/JCO.18.02424 |
[34] |
DAVIS J L, THEORET M R, ZHENG Z L, et al. Development of human anti-murine T-cell receptor antibodies in both responding and nonresponding patients enrolled in TCR gene therapy trials[J]. Clin Cancer Res, 2010, 16(23): 5852-5861.
doi: 10.1158/1078-0432.CCR-10-1280 pmid: 21138872 |
[35] | KERNEL N N I. TCR-redirected T cells therapy in patient with HBV related HCC[J]. Case Med Res, 2019.[Epub ahead of print]. |
[36] |
SPEAR T T, EVAVOLD B D, BAKER B M, et al. Understanding TCR affinity, antigen specificity, and cross-reactivity to improve TCR gene-modified T cells for cancer immunotherapy[J]. Cancer Immunol Immunother, 2019, 68(11): 1881-1889.
doi: 10.1007/s00262-019-02401-0 pmid: 31595324 |
[37] |
SANDERSON J P, CROWLEY D J, WIEDERMANN G E, et al. Preclinical evaluation of an affinity-enhanced MAGE-A4-specific T-cell receptor for adoptive T-cell therapy[J]. Oncoimmunology, 2020, 9(1): 1682381.
doi: 10.1080/2162402X.2019.1682381 |
[38] |
KHONG H T, WANG Q J, ROSENBERG S A. Identification of multiple antigens recognized by tumor-infiltrating lymphocytes from a single patient: tumor escape by antigen loss and loss of MHC expression[J]. J Immunother, 2004, 27(3): 184-190.
doi: 10.1097/00002371-200405000-00002 pmid: 15076135 |
[39] |
NATHAN P, HASSEL J C, RUTKOWSKI P, et al. Overall survival benefit with tebentafusp in metastatic uveal melanoma[J]. N Engl J Med, 2021, 385(13): 1196-1206.
doi: 10.1056/NEJMoa2103485 |
[40] |
WALKER A J, MAJZNER R G, ZHANG L, et al. Tumor antigen and receptor densities regulate efficacy of a chimeric antigen receptor targeting anaplastic lymphoma kinase[J]. Mol Ther, 2017, 25(9): 2189-2201.
doi: S1525-0016(17)30270-8 pmid: 28676342 |
[41] |
ROBINSON J, HALLIWELL J A, HAYHURST J D, et al. The IPD and IMGT/HLA database: allele variant databases[J]. Nucleic Acids Res, 2015, 43(Database issue): D423-D431.
doi: 10.1093/nar/gku1161 |
[42] | GONZALEZ-GALARZA F F, MCCABE A, SANTOS E J M D, et al. Allele frequency net database (AFND) 2020 update: gold-standard data classification, open access genotype data and new query tools[J]. Nucleic Acids Res, 2020, 48(D1): D783-D788. |
[43] |
GARETTO S, SARDI C, MARTINI E, et al. Tailored chemokine receptor modification improves homing of adoptive therapy T cells in a spontaneous tumor model[J]. Oncotarget, 2016, 7(28): 43010-43026.
doi: 10.18632/oncotarget.9280 pmid: 27177227 |
[44] | IDORN M, SKADBORG S K, KELLERMANN L, et al. Chemokine receptor engineering of T cells with CXCR2 improves homing towards subcutaneous human melanomas in xenograft mouse model[J]. Oncoimmunology, 2018, 7(8): e1450715. |
[45] |
HU J M, SUN C, BERNATCHEZ C, et al. T-cell homing therapy for reducing regulatory T cells and preserving effector T-cell function in large solid tumors[J]. Clin Cancer Res, 2018, 24(12): 2920-2934.
doi: 10.1158/1078-0432.CCR-17-1365 pmid: 29391351 |
[46] |
ADACHI K, KANO Y, NAGAI T, et al. IL-7 and CCL19 expression in CAR-T cells improves immune cell infiltration and CAR-T cell survival in the tumor[J]. Nat Biotechnol, 2018, 36(4): 346-351.
doi: 10.1038/nbt.4086 pmid: 29505028 |
[47] |
FRAIETTA J A, LACEY S F, ORLANDO E J, et al. Author correction: determinants of response and resistance to CD19 chimeric antigen receptor (CAR) T cell therapy of chronic lymphocytic leukemia[J]. Nat Med, 2021, 27(3): 561.
doi: 10.1038/s41591-021-01248-2 pmid: 33547459 |
[48] |
BECHMAN N, MAHER J. Lymphodepletion strategies to potentiate adoptive T-cell immunotherapy-what are we doing; where are we going?[J]. Expert Opin Biol Ther, 2021, 21(5): 627-637.
doi: 10.1080/14712598.2021.1857361 |
[49] | CHEN J, SUN H W, YANG Y Y, et al. Reprogramming immunosuppressive myeloid cells by activated T cells promotes the response to anti-PD-1 therapy in colorectal cancer[J]. Signal Transduct Target Ther, 2021, 6(1): 4. |
[50] |
KIM J, KANG S, KIM K W, et al. Nanoparticle delivery of recombinant IL-2 (BALLkine-2) achieves durable tumor control with less systemic adverse effects in cancer immunotherapy[J]. Biomaterials, 2022, 280: 121257.
doi: 10.1016/j.biomaterials.2021.121257 |
[51] |
SAKAI T, TERAKURA S, MIYAO K, et al. Artificial T cell adaptor molecule-transduced TCR-T cells demonstrated improved proliferation only when transduced in a higher intensity[J]. Mol Ther Oncolytics, 2020, 18: 613-622.
doi: 10.1016/j.omto.2020.08.014 |
[52] |
ROTH T L, LI P J, BLAESCHKE F, et al. Pooled knockin targeting for genome engineering of cellular immunotherapies[J]. Cell, 2020, 181(3): 728-744.e21.
doi: S0092-8674(20)30332-9 pmid: 32302591 |
[53] |
MARTINEZ M, MOON E K. CAR T cells for solid tumors: New strategies for finding, infiltrating, and surviving in the tumor microenvironment[J]. Front Immunol, 2019, 10: 128.
doi: 10.3389/fimmu.2019.00128 pmid: 30804938 |
[54] |
NALAWADE S A, SHAFER P, BAJGAIN P, et al. Selectively targeting myeloid-derived suppressor cells through TRAIL receptor 2 to enhance the efficacy of CAR T cell therapy for treatment of breast cancer[J]. J Immunother Cancer, 2021, 9(11): e003237.
doi: 10.1136/jitc-2021-003237 |
[55] |
LIN S H, CHENG L, YE W, et al. Chimeric CTLA4-CD28-CD3z T cells potentiate antitumor activity against CD80/CD86-positive B cell malignancies[J]. Front Immunol, 2021, 12: 642528.
doi: 10.3389/fimmu.2021.642528 |
[56] |
NEWICK K, O'BRIEN S, MOON E, et al. CAR T cell therapy for solid tumors[J]. Annu Rev Med, 2017, 68: 139-152.
doi: 10.1146/annurev-med-062315-120245 pmid: 27860544 |
[57] |
D’ALOIA M M, ZIZZARI I G, SACCHETTI B, et al. CAR-T cells: the long and winding road to solid tumors[J]. Cell Death Dis, 2018, 9(3): 282.
doi: 10.1038/s41419-018-0278-6 pmid: 29449531 |
[58] |
ZHANG B L, QIN D Y, MO Z M, et al. Hurdles of CAR-T cell-based cancer immunotherapy directed against solid tumors[J]. Sci China Life Sci, 2016, 59(4): 340-348.
doi: 10.1007/s11427-016-5027-4 |
[59] |
YE B X, SMERIN D, GAO Q P, et al. High-throughput sequencing of the immune repertoire in oncology: applications for clinical diagnosis, monitoring, and immunotherapies[J]. Cancer Lett, 2018, 416: 42-56.
doi: S0304-3835(17)30789-9 pmid: 29247824 |
[60] |
CHEN F J, ZOU Z Y, DU J, et al. Neoantigen identification strategies enable personalized immunotherapy in refractory solid tumors[J]. J Clin Invest, 2019, 129(5): 2056-2070.
doi: 10.1172/JCI99538 pmid: 30835255 |
[61] |
JOGLEKAR A V, LEONARD M T, JEPPSON J D, et al. T cell antigen discovery via signaling and antigen-presenting bifunctional receptors[J]. Nat Methods, 2019, 16(2): 191-198.
doi: 10.1038/s41592-018-0304-8 pmid: 30700902 |
[62] |
CHEN X J, PONCETTE L, BLANKENSTEIN T. Human TCR-MHC coevolution after divergence from mice includes increased nontemplate-encoded CDR3 diversity[J]. J Exp Med, 2017, 214(11): 3417-3433.
doi: 10.1084/jem.20161784 |
[63] | KRSHNAN L, PARK S, IM W, et al. A conserved αβ transmembrane interface forms the core of a compact T-cell receptor-CD3 structure within the membrane[J]. Proc Natl Acad Sci U S A, 2016, 113(43): E6649-E6658. |
[64] |
KNIES D, KLOBUCH S, XUE S A, et al. An optimized single chain TCR scaffold relying on the assembly with the native CD3-complex prevents residual mispairing with endogenous TCRs in human T-cells[J]. Oncotarget, 2016, 7(16): 21199-21221.
doi: 10.18632/oncotarget.8385 pmid: 27028870 |
[65] |
ARMISTEAD P M. Cellular therapy against public neoantigens[J]. J Clin Invest, 2019, 129(2): 506-508.
doi: 10.1172/JCI126116 pmid: 30640175 |
[66] |
LU Y C, ZHENG Z L, LOWERY F J, et al. Direct identification of neoantigen-specific TCRs from tumor specimens by high-throughput single-cell sequencing[J]. J Immunother Cancer, 2021, 9(7): e002595.
doi: 10.1136/jitc-2021-002595 |
[67] |
LI S R, HUO F Y, WANG H Q, et al. Recent advances in porous nanomaterials-based drug delivery systems for cancer immunotherapy[J]. J Nanobiotechnology, 2022, 20(1): 277.
doi: 10.1186/s12951-022-01489-4 |
[68] |
CADILHA B L, BENMEBAREK M R, DORMAN K, et al. Combined tumor-directed recruitment and protection from immune suppression enable CAR T cell efficacy in solid tumors[J]. Sci Adv, 2021, 7(24): eabi5781.
doi: 10.1126/sciadv.abi5781 |
[69] |
EVGIN L, KOTTKE T, TONNE J, et al. Oncolytic virus-mediated expansion of dual-specific CAR T cells improves efficacy against solid tumors in mice[J]. Sci Transl Med, 2022, 14(640): eabn2231.
doi: 10.1126/scitranslmed.abn2231 |
[70] |
PARKHURST M, GROS A, PASETTO A, et al. Isolation of T-cell receptors specifically reactive with mutated tumor-associated antigens from tumor-infiltrating lymphocytes based on CD137 expression[J]. Clin Cancer Res, 2017, 23(10): 2491-2505.
doi: 10.1158/1078-0432.CCR-16-2680 pmid: 27827318 |
[71] |
MARCU A, BICHMANN L, KUCHENBECKER L, et al. HLA Ligand Atlas: a benign reference of HLA-presented peptides to improve T-cell-based cancer immunotherapy[J]. J Immunother Cancer, 2021, 9(4): e002071.
doi: 10.1136/jitc-2020-002071 |
[72] |
HU Z D, ZHU L Y, WANG J, et al. Immune signature of enhanced functional avidity CD8+ T cells in vivo induced by vaccinia vectored vaccine[J]. Sci Rep, 2017, 7: 41558.
doi: 10.1038/srep41558 |
[73] |
ALBA J, D‘ABRAMO M. The full model of the pMHC-TCR-CD3 complex: a structural and dynamical characterization of bound and unbound states[J]. Cells, 2022, 11(4): 668.
doi: 10.3390/cells11040668 |
[74] |
HE W H, CAO Z L, MAO F F, et al. Modification of three amino acids in sodium taurocholate cotransporting polypeptide renders mice susceptible to infection with hepatitis D virus in vivo[J]. J Virol, 2016, 90(19): 8866-8874.
doi: 10.1128/JVI.00901-16 |
[75] |
CAO Y Q, LU W Y, SUN R, et al. Anti-CD19 chimeric antigen receptor T cells in combination with nivolumab are safe and effective against relapsed/refractory B-cell non-Hodgkin lymphoma[J]. Front Oncol, 2019, 9: 767.
doi: 10.3389/fonc.2019.00767 pmid: 31482064 |
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