TIM-3, a promising target for cancer immunotherapy

Figures & data

Table 1 TIM-3 and cancer

Year	Diseases	Conclusions	References
2010	Solid tumors	Combined TIM-3 with PD-1 inhibitor could prevent tumor progression.	^Citation19
2010	Melanoma	TIM-3/TIM-3L inhibitor combined with PD-1/PD-L1 inhibitor could reverse T-cell exhaustion and/or dysfunction in advanced melanoma.	^Citation43
2011	Cancer	Anti-TIM-3 molecular antibody suppressed tumors by promoting T-cell IFN-γ- mediated antitumor immunity.	^Citation44
2011	AML	Combined PD-1/PD-L1 with TIM-3/Gal-9 blockade could prevent CD8^+ T-cell exhaustion in advanced AML.	^Citation18
2013	AML	In xenograft models, anti-TIM-3 IgG2a antibody could improve cytotoxic activities and eradicate AML leukemic stem cells.	^Citation45
2013	Melanoma	Combined anti-TIM-3 with anti-TIM-4 molecule antibodies could increase the antitumor responses in vivo.	^Citation46
2013	Ovarian cancer	Combined anti-TIM-3 and CD137 molecule antibodies significantly inhibited tumor progression.	^Citation47
2014	Melanoma	PD-1 combined with TIM-3 blockades could stimulate potential antitumor T-cell responses in melanoma.	^Citation48
2015	Gastric cancer	Combined treatments of TIM-3 and CD137, TIM-3 and PD-1, and TIM-3 and CEACAM1 could enhance immune cell response in progression stage cancer. And anti-TIM-3 and anti-TIM-4 molecule antibodies could increase cancer vaccine’s efficacy.	^Citation49
2015	RCC	TIM-3 expressed on myeloid cells played a critical role in augmenting tumorigenic activities of TIM-3-negative RCC cells. Anti-TIM-3 monoclonal antibody suppressed the cancer cells.	^Citation41
2015	Colon cancer	Gal-9/TIM-3 blockade could inhibit the tumor progression in vivo. The blockade increased therapeutic efficacy of cyclophosphamide.	^Citation50
2015	Colon cancer	TIM-3 was correlated with colon cancer immune escape.	^Citation26
2015	Lung adenocarcinoma	TIM-3 could express on NK cells and was a potential new immune therapy target.	^Citation22
2015	Colorectal carcinoma	Higher expression of TIM-3 indicated restriction of T-cell responses.	^Citation27
2015	Gastric cancer	TIM-3 expression was correlated with the stages of gastric cancer and was regulated by T-bet.	^Citation36
2016	RCC	Blocking the TIM-3 pathway reversed cell proliferation and increased IFN-γ production in varied types of T cell.	^Citation17
2016	Colorectal carcinoma	TIM-3/TIM-3L and PD-1/PD-L1 blockade reversed T-cell dysfunction and exhaustion in colorectal cancer.	^Citation51
2016	Glioma	Gal-9/TIM-3 pathway was important in immune evasion and could be a potential target in glioma.	^Citation33
2017	AML	TIM-3/Gal-9 was a reliable target for AML immune therapy.	^Citation20
2017	HCC	Antibodies against PD-L1, TIM-3, or LAG-3 restored responses of HCC-derived T cells to tumor antigens.	^Citation52
2017	Gastric cancer	Dual blockade of TIM-3 and PD-1 could improve antitumor function of cancer CD8^+ T cells.	^Citation53
2017	Colorectal cancer	TIM-3 was correlated with the progression of colorectal cancer and could be a potential therapeutic target.	^Citation25
2017	Prostate cancer	TIM-3 inhibited the immune response in prostate cancer and could be a potential therapeutic target.	^Citation40

Abbreviations: TIM-3, T cell immunoglobulin mucin-3; TIM-3L, T cell immunoglobulin mucinligand 3; PD-1, programmed cell death protein-1; PD-L1, programmed cell death protein-ligand 1; IFN-γ, interferon-γ; Gal-9, galectin-9; AML, acute myeloid leukemia; RCC, renal cell carcinoma; NK, nature killer; HCC, Hepatocellular carcinoma; LAG-3, lymphocyte-activation gene-3.

Table 2 Clinical trials of TIM-3 inhibitors

Year	Drug	Phase	Company	Type	Objective	ClinicalTrial.gov identifier
2015	MBG453	I	Novartis Pharmaceuticals (Basel, Switzerland)	Anti-TIM-3	MBG453 given alone or combined with PDR001 in adult patients with advanced malignancies	NCT2608268
2016	TSR-022	I	Tesaro, Inc. (Waltham, MA, USA)	Anti-TIM-3	Dose escalation and cohort expansion study of TSR-022 in advanced solid tumors	NCT2817633
2017	LY3321367	I	Eli Lilly and Company (Indianapolis, IN, USA)	Anti-TIM-3	LY3321367 alone or combined with an anti-PD-L1 antibody in advanced relapsed/refractory solid tumors	NCT3099109
2017	MBG453	I	Novartis Pharmaceuticals	Anti-TIM-3	PDR001 and/or MBG453 in combination with decitabine in AML or high-risk MDS	NCT3066648

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