Chimeric Antigen Receptor Cell Therapy: Overcoming Obstacles to Battle Cancer

被引:23
作者
Petty, Amy J. [1 ]
Heyman, Benjamin [2 ]
Yang, Yiping [3 ]
机构
[1] Duke Univ, Dept Pharmacol & Canc Biol, Durham, NC 27710 USA
[2] Univ Calif San Diego, Dept Med, Div Regenerat Med, La Jolla, CA 92093 USA
[3] Ohio State Univ, Div Hematol, Columbus, OH 43210 USA
基金
美国国家卫生研究院;
关键词
CAR-T cells; CAR-NK cells; CAR-NKT cells; cancer immunotherapy; solid tumors; hematologic malignancies; genetic engineering; novel approaches; CAR-T-CELLS; NATURAL-KILLER-CELLS; IN-VIVO EXPANSION; B-CELL; ADOPTIVE IMMUNOTHERAPY; 4-1BB COSTIMULATION; CD19; LYMPHOMA; ACTIVATION; NEUROTOXICITY;
D O I
10.3390/cancers12040842
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Chimeric antigen receptors (CAR) are fusion proteins engineered from antigen recognition, signaling, and costimulatory domains that can be used to reprogram T cells to specifically target tumor cells expressing specific antigens. Current CAR-T cell technology utilizes the patient's own T cells to stably express CARs and has achieved exciting clinical success in the past few years. However, current CAR-T cell therapy still faces several challenges, including suboptimal persistence and potency, impaired trafficking to solid tumors, local immunosuppression within the tumor microenvironment and intrinsic toxicity associated with CAR-T cells. This review focuses on recent strategies to improve the clinical efficacy of CAR-T cell therapy and other exciting CAR approaches currently under investigation, including CAR natural killer (NK) and NKT cell therapies.
引用
收藏
页数:17
相关论文
共 110 条
  • [1] Updated safety and long term clinical outcomes in TRANSCEND NHL 001, pivotal trial of lisocabtagene maraleucel (JCAR017) in R/R aggressive NHL.
    Abramson, Jeremy S.
    Gordon, Leo I.
    Palomba, Maria Lia
    Lunning, Matthew Alexander
    Arnason, Jon E.
    Forero-Torres, Andres
    Wang, Michael
    Maloney, David G.
    Sehgal, Alison
    Andreadis, Charalambos
    Purev, Enkhtsetseg
    Solomon, Scott R.
    Ghosh, Nilanjan
    Albertson, Tina M.
    Xie, Benhuai
    Garcia, Jacob
    Siddiqi, Tanya
    [J]. JOURNAL OF CLINICAL ONCOLOGY, 2018, 36 (15)
  • [2] High durable CR rates and preliminary safety profile for JCAR017 in R/R aggressive b-NHL (TRANSCEND NHL 001 Study): A defined composition CD19-directed CAR T-cell product with potential for outpatient administration.
    Abramson, Jeremy S.
    Siddiqi, Tanya
    Palomba, Maria Lia
    Gordon, Leo I.
    Lunning, Matthew Alexander
    Arnason, Jon E.
    Wang, Michael
    Forero-Torres, Andres
    Albertson, Tina
    Dehner, Christine
    Garcia, Jacob
    Li, Daniel
    Xie, Benhuai
    Maloney, David G.
    [J]. JOURNAL OF CLINICAL ONCOLOGY, 2018, 36 (05)
  • [3] Regional delivery of mesothelin-targeted CAR T cells for pleural cancers: Safety and preliminary efficacy in combination with anti-PD-1 agent.
    Adusumilli, Prasad S.
    Zauderer, Marjorie Glass
    Rusch, Valerie W.
    O'Cearbhaill, Roisin
    Zhu, Amy
    Ngai, Daniel
    McGee, Erin
    Chintala, Navin
    Messinger, John
    Cheema, Waseem
    Halton, Elizabeth
    Diamonte, Claudia
    Pineda, John
    Vincent, Alain
    Modi, Shanu
    Solomon, Stephen Barnett
    Jones, David Randolph
    Brentjens, Renier J.
    Riviere, Isabelle
    Sadelain, Michel
    [J]. JOURNAL OF CLINICAL ONCOLOGY, 2019, 37 (15)
  • [4] Regional delivery of mesothelin-targeted CAR T cell therapy generates potent and long-lasting CD4-dependent tumor immunity
    Adusumilli, Prasad S.
    Cherkassky, Leonid
    Villena-Vargas, Jonathan
    Colovos, Christos
    Servais, Elliot
    Plotkin, Jason
    Jones, David R.
    Sadelain, Michel
    [J]. SCIENCE TRANSLATIONAL MEDICINE, 2014, 6 (261)
  • [5] HER2-Specific Chimeric Antigen Receptor-Modified Virus-Specific T Cells for Progressive Glioblastoma A Phase 1 Dose-Escalation Trial
    Ahmed, Nabil
    Brawley, Vita
    Hegde, Meenakshi
    Bielamowicz, Kevin
    Kalra, Mamta
    Landi, Daniel
    Robertson, Catherine
    Gray, Tara L.
    Diouf, Oumar
    Wakefield, Amanda
    Ghazi, Alexia
    Gerken, Claudia
    Yi, Zhongzhen
    Ashoori, Aidin
    Wu, Meng-Fen
    Liu, Hao
    Rooney, Cliona
    Dotti, Gianpietro
    Gee, Adrian
    Su, Jack
    Kew, Yvonne
    Baskin, David
    Zhang, Yi Jonathan
    New, Pamela
    Grilley, Bambi
    Stojakovic, Milica
    Hicks, John
    Powell, Suzanne Z.
    Brenner, Malcolm K.
    Heslop, Helen E.
    Grossman, Robert
    Wels, Winfried S.
    Gottschalk, Stephen
    [J]. JAMA ONCOLOGY, 2017, 3 (08) : 1094 - 1101
  • [6] Function of Novel Anti-CD19 Chimeric Antigen Receptors with Human Variable Regions Is Affected by Hinge and Transmembrane Domains
    Alabanza, Leah
    Pegues, Melissa
    Geldres, Claudia
    Shi, Victoria
    Wiltzius, Jed J. W.
    Sievers, Stuart A.
    Yang, Shicheng
    Kochenderfer, James N.
    [J]. MOLECULAR THERAPY, 2017, 25 (11) : 2452 - 2465
  • [7] T cells expressing an anti-B-cell maturation antigen chimeric antigen receptor cause remissions of multiple myeloma
    Ali, Syed Abbas
    Shi, Victoria
    Maric, Irina
    Wang, Michael
    Stroncek, David F.
    Rose, Jeremy J.
    Brudno, Jennifer N.
    Stetler-Stevenson, Maryalice
    Feldman, Steven A.
    Hansen, Brenna G.
    Fellowes, Vicki S.
    Hakim, Frances T.
    Gress, Ronald E.
    Kochenderfer, James N.
    [J]. BLOOD, 2016, 128 (13) : 1688 - 1700
  • [8] CCL3 augments tumor rejection and enhances CD8+ T cell infiltration through NK and CD103+ dendritic cell recruitment via IFN
    Allen, Frederick
    Bobanga, Iuliana D.
    Rauhe, Peter
    Barkauskas, Deborah
    Teich, Nathan
    Tong, Caryn
    Myers, Jay
    Huang, Alex Y.
    [J]. ONCOIMMUNOLOGY, 2018, 7 (03):
  • [9] Simultaneous Targeting of CD19 and CD22: Phase I Study of AUTO3, a Bicistronic Chimeric Antigen Receptor (CAR) T-Cell Therapy, in Pediatric Patients with Relapsed/Refractory B-Cell Acute Lymphoblastic Leukemia (r/r B-ALL): Amelia Study
    Amrolia, Persis J.
    Wynn, Robert
    Hough, Rachael
    Vora, Ajay
    Bonney, Denise
    Veys, Paul
    Rao, Kanchan
    Chiesa, Robert
    Al-Hajj, Muhammad
    Cordoba, Shaun P.
    Onuoha, Shimobi
    Kotsopoulou, Ekaterini
    Khokhar, Nushmia Z.
    Pule, Martin
    Peddareddigari, Vijay G. R.
    [J]. BLOOD, 2018, 132
  • [10] The biology of NKT cells
    Bendelac, Albert
    Savage, Paul B.
    Teyton, Luc
    [J]. ANNUAL REVIEW OF IMMUNOLOGY, 2007, 25 : 297 - 336