Review
. 2016 Apr; 9:1767-76.
doi: 10.2147/OTT.S65802.

Tremelimumab: research and clinical development

Begoña Comin-Anduix 1 Helena Escuin-Ordinas 2 Francisco Javier Ibarrondo 3 
Affiliations
  • PMID: 27042127
  •     62 References
  •     27 citations

Abstract

The immune checkpoint therapy is a relatively recent strategy that aims to tweak the immune system to effectively attack cancer cells. The understanding of the immune responses and their regulation at the intracellular level and the development of fully humanized monoclonal antibodies are the pillars of an approach that could elicit durable clinical responses and even remission in some patients with cancer. Most of the immune checkpoints that regulate the T-cell responses (activation and inhibition) operate through proteins present on the cytoplasmic membrane of the immune cells. Therefore, specific antibodies capable of blocking the inhibitory signals should lead to unrestrained immune responses that supersede the inhibitory mechanisms, which are naturally present in the tumor microenviroment. The best-known and most successful targets for immune checkpoint therapy are the cytotoxic T-lymphocyte antigen-4 and programmed cell death-1 coreceptors. Tremelimumab (CP-675,206) is a fully humanized monoclonal antibody specific for cytotoxic T-lymphocyte antigen-4, which has been successfully used to treat patients with metastatic melanoma and some other cancers. Although still a work in progress, the use of tremelimumab as an immune checkpoint therapeutic agent is a promising approach alone or in combination with other anticancer drugs. Here, we review the use of this antibody in a number of clinical trials against solid tumors.

Keywords: anti-CTLA-4 blockade antibody; cancer; immune checkpoint.

Efficacy and safety of an intensified schedule of tremelimumab for chemotherapy-resistant malignant mesothelioma: an open-label, single-arm, phase 2 study.
Luana Calabrò, Aldo Morra, +10 authors, Michele Maio.
Lancet Respir Med, 2015 Mar 31; 3(4). PMID: 25819643
Phase I/II trial of tremelimumab in patients with metastatic melanoma.
Luis H Camacho, Scott Antonia, +8 authors, Antoni Ribas.
J Clin Oncol, 2009 Jan 14; 27(7). PMID: 19139427
Immune checkpoint targeting in cancer therapy: toward combination strategies with curative potential.
Padmanee Sharma, James P Allison.
Cell, 2015 Apr 11; 161(2). PMID: 25860605    Free PMC article.
Highly Cited. Review.
Modulation of lymphocyte regulation for cancer therapy: a phase II trial of tremelimumab in advanced gastric and esophageal adenocarcinoma.
Christy Ralph, Eyad Elkord, +5 authors, Fiona C Thistlethwaite.
Clin Cancer Res, 2010 Feb 25; 16(5). PMID: 20179239
Intratumoral immune cell infiltrates, FoxP3, and indoleamine 2,3-dioxygenase in patients with melanoma undergoing CTLA4 blockade.
Antoni Ribas, Begoña Comin-Anduix, +9 authors, Alistair J Cochran.
Clin Cancer Res, 2009 Jan 02; 15(1). PMID: 19118070
CTLA4 blockade induces frequent tumor infiltration by activated lymphocytes regardless of clinical responses in humans.
Rong Rong Huang, Jason Jalil, +10 authors, Antoni Ribas.
Clin Cancer Res, 2011 May 12; 17(12). PMID: 21558401    Free PMC article.
Tremelimumab for patients with chemotherapy-resistant advanced malignant mesothelioma: an open-label, single-arm, phase 2 trial.
Luana Calabrò, Aldo Morra, +8 authors, Michele Maio.
Lancet Oncol, 2013 Sep 17; 14(11). PMID: 24035405
Highly Cited.
CD28 and CTLA-4 coreceptor expression and signal transduction.
Christopher E Rudd, Alison Taylor, Helga Schneider.
Immunol Rev, 2009 May 12; 229(1). PMID: 19426212    Free PMC article.
Highly Cited. Review.
Phase I trial of tremelimumab in combination with short-term androgen deprivation in patients with PSA-recurrent prostate cancer.
Douglas G McNeel, Heath A Smith, +4 authors, Glenn Liu.
Cancer Immunol Immunother, 2012 Jan 03; 61(7). PMID: 22210552    Free PMC article.
Phase II trial of tremelimumab (CP-675,206) in patients with advanced refractory or relapsed melanoma.
John M Kirkwood, Paul Lorigan, +7 authors, Cecile A Bulanhagui.
Clin Cancer Res, 2010 Jan 21; 16(3). PMID: 20086001
Long term survival with cytotoxic T lymphocyte-associated antigen 4 blockade using tremelimumab.
Zeynep Eroglu, Dae Won Kim, +9 authors, Antoni Ribas.
Eur J Cancer, 2015 Sep 15; 51(17). PMID: 26364516    Free PMC article.
T-cell antigen CD28 mediates adhesion with B cells by interacting with activation antigen B7/BB-1.
P S Linsley, E A Clark, J A Ledbetter.
Proc Natl Acad Sci U S A, 1990 Jul 01; 87(13). PMID: 2164219    Free PMC article.
Highly Cited.
Safety, activity, and immune correlates of anti-PD-1 antibody in cancer.
Suzanne L Topalian, F Stephen Hodi, +27 authors, Mario Sznol.
N Engl J Med, 2012 Jun 05; 366(26). PMID: 22658127    Free PMC article.
Highly Cited.
FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer.
Thierry Conroy, Françoise Desseigne, +19 authors, PRODIGE Intergroup.
N Engl J Med, 2011 May 13; 364(19). PMID: 21561347
Highly Cited.
CTLA-4-mediated inhibition in regulation of T cell responses: mechanisms and manipulation in tumor immunotherapy.
C A Chambers, M S Kuhns, J G Egen, J P Allison.
Annu Rev Immunol, 2001 Mar 13; 19. PMID: 11244047
Highly Cited. Review.
Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine.
Daniel D Von Hoff, Thomas Ervin, +20 authors, Markus F Renschler.
N Engl J Med, 2013 Oct 18; 369(18). PMID: 24131140    Free PMC article.
Highly Cited.
Guidelines for the evaluation of immune therapy activity in solid tumors: immune-related response criteria.
Jedd D Wolchok, Axel Hoos, +9 authors, F Stephen Hodi.
Clin Cancer Res, 2009 Nov 26; 15(23). PMID: 19934295
Highly Cited.
The future of immune checkpoint therapy.
Padmanee Sharma, James P Allison.
Science, 2015 Apr 04; 348(6230). PMID: 25838373
Highly Cited. Review.
Identification of an alternative CTLA-4 ligand costimulatory for T cell activation.
K S Hathcock, G Laszlo, +3 authors, R J Hodes.
Science, 1993 Nov 05; 262(5135). PMID: 7694361
Highly Cited.
Uncovering of functional alternative CTLA-4 counter-receptor in B7-deficient mice.
G J Freeman, F Borriello, +7 authors, D B Lombard.
Science, 1993 Nov 05; 262(5135). PMID: 7694362
Highly Cited.
Natural killer T cells in advanced melanoma patients treated with tremelimumab.
F Javier Ibarrondo, Otto O Yang, +11 authors, Begoña Comin-Anduix.
PLoS One, 2013 Oct 30; 8(10). PMID: 24167550    Free PMC article.
Enhancement of antitumor immunity by CTLA-4 blockade.
D R Leach, M F Krummel, J P Allison.
Science, 1996 Mar 22; 271(5256). PMID: 8596936
Highly Cited.
Pooled Analysis of Long-Term Survival Data From Phase II and Phase III Trials of Ipilimumab in Unresectable or Metastatic Melanoma.
Dirk Schadendorf, F Stephen Hodi, +7 authors, Jedd D Wolchok.
J Clin Oncol, 2015 Feb 11; 33(17). PMID: 25667295    Free PMC article.
Highly Cited.
Detailed analysis of immunologic effects of the cytotoxic T lymphocyte-associated antigen 4-blocking monoclonal antibody tremelimumab in peripheral blood of patients with melanoma.
Begoña Comin-Anduix, Yohan Lee, +13 authors, Antoni Ribas.
J Transl Med, 2008 May 03; 6. PMID: 18452610    Free PMC article.
Phase II study of the anti-cytotoxic T-lymphocyte-associated antigen 4 monoclonal antibody, tremelimumab, in patients with refractory metastatic colorectal cancer.
Ki Y Chung, Ira Gore, +8 authors, Leonard B Saltz.
J Clin Oncol, 2010 May 26; 28(21). PMID: 20498386
The blockade of immune checkpoints in cancer immunotherapy.
Drew M Pardoll.
Nat Rev Cancer, 2012 Mar 23; 12(4). PMID: 22437870    Free PMC article.
Highly Cited. Review.
Improved survival with ipilimumab in patients with metastatic melanoma.
F Stephen Hodi, Steven J O'Day, +26 authors, Walter J Urba.
N Engl J Med, 2010 Jun 08; 363(8). PMID: 20525992    Free PMC article.
Highly Cited.
CD28/B7 system of T cell costimulation.
D J Lenschow, T L Walunas, J A Bluestone.
Annu Rev Immunol, 1996 Jan 01; 14. PMID: 8717514
Highly Cited. Review.
A phase I dose escalation trial of tremelimumab (CP-675,206) in combination with gemcitabine in chemotherapy-naive patients with metastatic pancreatic cancer.
M Aglietta, C Barone, +10 authors, F Leone.
Ann Oncol, 2014 Jun 08; 25(9). PMID: 24907635
Development of TLR9 agonists for cancer therapy.
Arthur M Krieg.
J Clin Invest, 2007 May 04; 117(5). PMID: 17476348    Free PMC article.
Highly Cited. Review.
Do we need a different set of response assessment criteria for tumor immunotherapy?
Antoni Ribas, Bartosz Chmielowski, John A Glaspy.
Clin Cancer Res, 2009 Nov 26; 15(23). PMID: 19934296
A clinical trial of CTLA-4 blockade with tremelimumab in patients with hepatocellular carcinoma and chronic hepatitis C.
Bruno Sangro, Carlos Gomez-Martin, +11 authors, Jesús Prieto.
J Hepatol, 2013 Mar 08; 59(1). PMID: 23466307
Highly Cited.
Ipilimumab plus dacarbazine for previously untreated metastatic melanoma.
Caroline Robert, Luc Thomas, +21 authors, Jedd D Wolchok.
N Engl J Med, 2011 Jun 07; 364(26). PMID: 21639810
Highly Cited.
Costimulation of T lymphocytes: the role of CD28, CTLA-4, and B7/BB1 in interleukin-2 production and immunotherapy.
R H Schwartz.
Cell, 1992 Dec 24; 71(7). PMID: 1335362
Highly Cited. Review.
Phenotypic characterization of CD8(+)NKT cells.
M Emoto, J Zerrahn, +2 authors, S H Kaufmann.
Eur J Immunol, 2000 Aug 15; 30(8). PMID: 10940921
Activating Fc γ receptors contribute to the antitumor activities of immunoregulatory receptor-targeting antibodies.
Yannick Bulliard, Rose Jolicoeur, +6 authors, Jennifer L Brogdon.
J Exp Med, 2013 Jul 31; 210(9). PMID: 23897982    Free PMC article.
Highly Cited.
CTLA4 blockade and GM-CSF combination immunotherapy alters the intratumor balance of effector and regulatory T cells.
Sergio A Quezada, Karl S Peggs, Michael A Curran, James P Allison.
J Clin Invest, 2006 Jun 17; 116(7). PMID: 16778987    Free PMC article.
Highly Cited.
OX40 engagement depletes intratumoral Tregs via activating FcγRs, leading to antitumor efficacy.
Yannick Bulliard, Rose Jolicoeur, +3 authors, Jennifer L Brogdon.
Immunol Cell Biol, 2014 Apr 16; 92(6). PMID: 24732076
Highly Cited.
Assessing oncologic benefit in clinical trials of immunotherapy agents.
R K Hales, J Banchereau, +4 authors, C G Drake.
Ann Oncol, 2010 Mar 20; 21(10). PMID: 20237004
Review.
Hurdles in therapy with regulatory T cells.
Piotr Trzonkowski, Rosa Bacchetta, +18 authors, Birgit Sawitzki.
Sci Transl Med, 2015 Sep 12; 7(304). PMID: 26355029
Highly Cited. Review.
B70 antigen is a second ligand for CTLA-4 and CD28.
M Azuma, D Ito, +4 authors, C Somoza.
Nature, 1993 Nov 04; 366(6450). PMID: 7694153
Highly Cited.
Meta-analysis of phase II cooperative group trials in metastatic stage IV melanoma to determine progression-free and overall survival benchmarks for future phase II trials.
Edward L Korn, Ping-Yu Liu, +11 authors, John M Kirkwood.
J Clin Oncol, 2008 Feb 01; 26(4). PMID: 18235113
Highly Cited.
Principles and use of anti-CTLA4 antibody in human cancer immunotherapy.
Karl S Peggs, Sergio A Quezada, Alan J Korman, James P Allison.
Curr Opin Immunol, 2006 Feb 09; 18(2). PMID: 16464564
Highly Cited. Review.
Antitumor activity in melanoma and anti-self responses in a phase I trial with the anti-cytotoxic T lymphocyte-associated antigen 4 monoclonal antibody CP-675,206.
Antoni Ribas, Luis H Camacho, +10 authors, Jesus Gomez-Navarro.
J Clin Oncol, 2005 Oct 06; 23(35). PMID: 16204013
Highly Cited.
Distinct immunological mechanisms of CTLA-4 and PD-1 blockade revealed by analyzing TCR usage in blood lymphocytes.
Lidia Robert, Christina Harview, +8 authors, Antoni Ribas.
Oncoimmunology, 2014 Aug 02; 3. PMID: 25083336    Free PMC article.
Phase I study of tremelimumab (CP-675 206) plus PF-3512676 (CPG 7909) in patients with melanoma or advanced solid tumours.
M Millward, C Underhill, +6 authors, C B Mather.
Br J Cancer, 2013 May 09; 108(10). PMID: 23652314    Free PMC article.
Breakthrough of the year 2013. Cancer immunotherapy.
Jennifer Couzin-Frankel.
Science, 2013 Dec 21; 342(6165). PMID: 24357284
Highly Cited.
Tremelimumab-associated tumor regression following after initial progression: two case reports.
Akihiko Shimomura, Yutaka Fujiwara, +6 authors, Noboru Yamamoto.
Immunotherapy, 2015 Oct 03; 8(1). PMID: 26427600
Safety and efficacy of combination immunotherapy with interferon alfa-2b and tremelimumab in patients with stage IV melanoma.
Ahmad A Tarhini, John Cherian, +5 authors, John M Kirkwood.
J Clin Oncol, 2011 Dec 21; 30(3). PMID: 22184371    Free PMC article.
CTLA4 blockade in mesothelioma: finally a competing strategy over cytotoxic/target therapy?
Luana Calabrò, Giovanni Luca Ceresoli, +4 authors, Michele Maio.
Cancer Immunol Immunother, 2014 Sep 23; 64(1). PMID: 25233793
Review.
Phase 1 dose-escalation trial of tremelimumab plus sunitinib in patients with metastatic renal cell carcinoma.
Brian I Rini, Mark Stein, +7 authors, Michael Gordon.
Cancer, 2010 Oct 06; 117(4). PMID: 20922784
Phase III randomized clinical trial comparing tremelimumab with standard-of-care chemotherapy in patients with advanced melanoma.
Antoni Ribas, Richard Kefford, +21 authors, Axel Hauschild.
J Clin Oncol, 2013 Jan 09; 31(5). PMID: 23295794    Free PMC article.
Highly Cited.
Sipuleucel-T immunotherapy for castration-resistant prostate cancer.
Philip W Kantoff, Celestia S Higano, +11 authors, IMPACT Study Investigators.
N Engl J Med, 2010 Sep 08; 363(5). PMID: 20818862
Highly Cited.
Tremelimumab for the treatment of malignant mesothelioma.
Alice Guazzelli, Michelle Hussain, Marija Krstic-Demonacos, Luciano Mutti.
Expert Opin Biol Ther, 2015 Nov 13; 15(12). PMID: 26560442
Review.
Tremelimumab in combination with exemestane in patients with advanced breast cancer and treatment-associated modulation of inducible costimulator expression on patient T cells.
Robert H Vonderheide, Patricia M LoRusso, +9 authors, Susan M Domchek.
Clin Cancer Res, 2010 May 19; 16(13). PMID: 20479064
Toll-like receptor 9 (TLR9) agonists in the treatment of cancer.
A M Krieg.
Oncogene, 2008 Jan 08; 27(2). PMID: 18176597
Highly Cited. Review.
Biologic and immunomodulatory events after CTLA-4 blockade with ticilimumab in patients with advanced malignant melanoma.
James M Reuben, Bang-Ning Lee, +7 authors, Luis H Camacho.
Cancer, 2006 Apr 15; 106(11). PMID: 16615096
Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer: a randomized trial.
H A Burris, M J Moore, +11 authors, D D Von Hoff.
J Clin Oncol, 1997 Jun 01; 15(6). PMID: 9196156
Highly Cited.
Modulation of cell signaling networks after CTLA4 blockade in patients with metastatic melanoma.
Begoña Comin-Anduix, Hooman Sazegar, +9 authors, Antoni Ribas.
PLoS One, 2010 Sep 22; 5(9). PMID: 20856802    Free PMC article.
Dendritic cell vaccination combined with CTLA4 blockade in patients with metastatic melanoma.
Antoni Ribas, Begoña Comin-Anduix, +15 authors, Jesus Gomez-Navarro.
Clin Cancer Res, 2009 Oct 01; 15(19). PMID: 19789309    Free PMC article.
Fc-dependent depletion of tumor-infiltrating regulatory T cells co-defines the efficacy of anti-CTLA-4 therapy against melanoma.
Tyler R Simpson, Fubin Li, +11 authors, Sergio A Quezada.
J Exp Med, 2013 Jul 31; 210(9). PMID: 23897981    Free PMC article.
Highly Cited.
Therapeutic use of anti-CTLA-4 antibodies.
Christian U Blank, Alexander Enk.
Int Immunol, 2014 Jul 20; 27(1). PMID: 25038057
Review.
Pharmacological interventions for melanoma: Comparative analysis using bayesian meta-analysis.
Yang Yang, Jiaomiao Pei, +4 authors, Jianhua Qiu.
Oncotarget, 2016 Oct 21; 7(49). PMID: 27764796    Free PMC article.
Review.
Structural basis of checkpoint blockade by monoclonal antibodies in cancer immunotherapy.
Ju Yeon Lee, Hyun Tae Lee, +11 authors, Yong-Seok Heo.
Nat Commun, 2016 Nov 01; 7. PMID: 27796306    Free PMC article.
Highly Cited.
Signaling by Antibodies: Recent Progress.
Stylianos Bournazos, Taia T Wang, +2 authors, Jeffrey V Ravetch.
Annu Rev Immunol, 2017 Apr 28; 35. PMID: 28446061    Free PMC article.
Highly Cited. Review.
Limitations and opportunities for immune checkpoint inhibitors in pediatric malignancies.
Jeong A Park, Nai-Kong V Cheung.
Cancer Treat Rev, 2017 Jun 18; 58. PMID: 28622628    Free PMC article.
Review.
Ongoing clinical trials of PD-1 and PD-L1 inhibitors for lung cancer in China.
Si-Yang Liu, Yi-Long Wu.
J Hematol Oncol, 2017 Jul 07; 10(1). PMID: 28679395    Free PMC article.
Review.
Fc Effector Function Contributes to the Activity of Human Anti-CTLA-4 Antibodies.
Frederick Arce Vargas, Andrew J S Furness, +32 authors, Sergio A Quezada.
Cancer Cell, 2018 Mar 27; 33(4). PMID: 29576375    Free PMC article.
Highly Cited.
T Cell Calcium Signaling Regulation by the Co-Receptor CD5.
Claudia M Tellez Freitas, Deborah K Johnson, K Scott Weber.
Int J Mol Sci, 2018 Apr 28; 19(5). PMID: 29701673    Free PMC article.
Review.
A mathematical modelling tool for unravelling the antibody-mediated effects on CTLA-4 interactions.
Aravindhan Ganesan, Theinmozhi Arulraj, Tahir Choulli, Khaled H Barakat.
BMC Med Inform Decis Mak, 2018 Jun 13; 18(1). PMID: 29890992    Free PMC article.
Immune Checkpoints and Innovative Therapies in Glioblastoma.
Massimo Romani, Maria Pia Pistillo, +2 authors, Barbara Banelli.
Front Oncol, 2018 Nov 09; 8. PMID: 30406030    Free PMC article.
Review.
Fatal myositis and spontaneous haematoma induced by combined immune checkpoint inhibitor treatment in a patient with pancreatic adenocarcinoma.
Yuan Liu, Zhi Liu, +4 authors, Xinlun Tian.
BMC Cancer, 2019 Dec 07; 19(1). PMID: 31805889    Free PMC article.
Blockade of CTLA-4 and Tim-3 pathways induces fetal loss with altered cytokine profiles by decidual CD4+T cells.
Songcun Wang, Chunqin Chen, +9 authors, Meirong Du.
Cell Death Dis, 2019 Jan 10; 10(1). PMID: 30622243    Free PMC article.
Immunogenicity of immunomodulatory, antibody-based, oncology therapeutics.
Jasmine Davda, Paul Declerck, +5 authors, Eugenia Kraynov.
J Immunother Cancer, 2019 Apr 18; 7(1). PMID: 30992085    Free PMC article.
Review.
Current Advances in the Treatment of BRAF-Mutant Melanoma.
Hima Patel, Nour Yacoub, +4 authors, Joan T Garrett.
Cancers (Basel), 2020 Feb 26; 12(2). PMID: 32092958    Free PMC article.
Review.
The Role of the Lymphocyte Functional Crosstalk and Regulation in the Context of Checkpoint Inhibitor Treatment-Review.
Barbara Seliger.
Front Immunol, 2019 Sep 27; 10. PMID: 31555274    Free PMC article.
Review.
How to select IgG subclasses in developing anti-tumor therapeutic antibodies.
Jifeng Yu, Yongping Song, Wenzhi Tian.
J Hematol Oncol, 2020 May 07; 13(1). PMID: 32370812    Free PMC article.
Review.
Adenovirus and Immunotherapy: Advancing Cancer Treatment by Combination.
Mizuho Sato-Dahlman, Christopher J LaRocca, Chikako Yanagiba, Masato Yamamoto.
Cancers (Basel), 2020 May 28; 12(5). PMID: 32455560    Free PMC article.
Review.
Intraductal Adaptation of the 4T1 Mouse Model of Breast Cancer Reveals Effects of the Epithelial Microenvironment on Tumor Progression and Metastasis.
Huda I Atiya, Anna Dvorkin-Gheva, +6 authors, Ann F Ramsdell.
Anticancer Res, 2019 May 17; 39(5). PMID: 31092419    Free PMC article.
Combination of Ipilimumab and Nivolumab in Cancers: From Clinical Practice to Ongoing Clinical Trials.
Omid Kooshkaki, Afshin Derakhshani, +6 authors, Behzad Baradaran.
Int J Mol Sci, 2020 Jun 26; 21(12). PMID: 32580338    Free PMC article.
Review.
Immune Checkpoint Inhibitors in Pediatric Solid Tumors: Status in 2018.
Tanvir F Kabir, Aman Chauhan, Lowell Anthony, Gerhard C Hildebrandt.
Ochsner J, 2018 Dec 19; 18(4). PMID: 30559623    Free PMC article.
Review.
Immune checkpoint inhibitor therapy for pediatric cancers: A mini review of endocrine adverse events.
Kenji Ihara.
Clin Pediatr Endocrinol, 2019 Aug 07; 28(3). PMID: 31384097    Free PMC article.
Oncolytic Viruses and Immune Checkpoint Inhibitors: Preclinical Developments to Clinical Trials.
June Kyu Hwang, JinWoo Hong, Chae-Ok Yun.
Int J Mol Sci, 2020 Nov 20; 21(22). PMID: 33207653    Free PMC article.
Review.
The State-of-the-Art of Phase II/III Clinical Trials for Targeted Pancreatic Cancer Therapies.
Andres Garcia-Sampedro, Gabriella Gaggia, +2 authors, Pilar Acedo.
J Clin Med, 2021 Feb 07; 10(4). PMID: 33546207    Free PMC article.
Review.
Pancreatic Cancer Signaling Pathways, Genetic Alterations, and Tumor Microenvironment: The Barriers Affecting the Method of Treatment.
Darya Javadrashid, Amir Baghbanzadeh, +5 authors, Behzad Baradaran.
Biomedicines, 2021 May 01; 9(4). PMID: 33918146    Free PMC article.
Review.
Immunotherapy Updates in Advanced Hepatocellular Carcinoma.
Amisha Singh, Ryan J Beechinor, +6 authors, May Cho.
Cancers (Basel), 2021 May 06; 13(9). PMID: 33946408    Free PMC article.
Review.
Durvalumab Plus Tremelimumab in Solid Tumors: A Systematic Review.
Caterina Arru, Maria Rosaria De Miglio, +4 authors, Panagiotis Paliogiannis.
Adv Ther, 2021 Jun 10; 38(7). PMID: 34105088    Free PMC article.
Systematic Review.
Leveraging the Treg-intrinsic CTLA4-PKCη signaling pathway for cancer immunotherapy.
Hsin-Yu Liu, Christophe Pedros, +3 authors, Amnon Altman.
J Immunother Cancer, 2021 Oct 01; 9(9). PMID: 34588224    Free PMC article.
Complementary roles of surgery and systemic treatment in clear cell renal cell carcinoma.
Alexandre Ingels, Riccardo Campi, +14 authors, Alexandre de la Taille.
Nat Rev Urol, 2022 May 14;. PMID: 35546184
Review.