Table 1 Selected Preclinical studies of anti-TIGIT agents in solid and hematological tumors
From: Targeting TIGIT for cancer immunotherapy: recent advances and future directions
Tumor types | Main treatment | Dose/Plan (Main treatment) | Object | Description | Other treatment included | Conditions |
|---|---|---|---|---|---|---|
Solid tumors | Anti-TIGIT (13G6) [122] | 250 μg/ twice weekly for 12 weeks (40w-52w) | HBs-HepR micea | Treatment with anti-TIGIT mAb delayed tumor growth, improved the overall survival, maintained a significant response and reinvigorated intrahepatic CD8+T cells with increased TNF-α and IFN-γ production and an increased number of CD8+T cells. | anti-PD-L1 (10F.9G2) | Hepatocellular Carcinoma |
TIGIT mAb (BE0274, Bio X Cell) [123] | 10 mg/kg i.p. three times a week from day 12 to day 40 | Tumor bearing Tgfbr1/Pten 2cKO mouse models after 5 consecutive days of tamoxifen administered | Treatment with anti-TIGIT slowed down the tumor progression with tolerable cytotoxicity, decreased the infiltration of Tregs, increased frequency of tumor-infiltrating CD8+ T cells and CD4+ T cells, and abrogated the immunosuppressive capacity of MDSCs relies on CD8+ T cells and Tregs. | PD-1 mAb (BE0146; Bio X Cell) | Head and Neck Squamous Cell Carcinoma | |
Ociperlimab (BGB-A1217 or BGB-A1217MF) Anti-mouse TIGIT mAb (mu10A7) [124] | 10 mg/kg (single agent) or 3 mg/kg (combination with anti-PD-1) i.p. every five days (Q5D) or 5 mg/kg i.p. every one week (QW) | CT26, MC38 or Renca bearing human TIGIT knock-in or BALB/c mouse model | Treatment with BGB-A1217 enhanced IFN-γ secretion of T cells, decreased the infiltration of Tregs, activated NK cells and monocytes and augmented T cell response and showed antineoplastic efficacy in combination with anti-PD-1. | Anti-mouse PD-1 antibody (Ch15mt) | Colon Cancer Kidney Cancer | |
COM902 [91] | 10 mg/kg (COM902 and anti-mPVRIG) and 3 mg/kg (anti-PD-L1) i.p. on day 6 (monotherapy) or day 8 (combination therapy) post tumor inoculation and dosed three times a week for two weeks | CT26 or Renca cells bearing female Balb/c mouse model | Chimeric COM902 combined with anti-PVRIG or anti-PD-L1 inhibited tumor growth and showed survival benefit. | Anti-PVRIG mAb (COM701) Anti-PD-L1 (Pembrolizuma) Anti-mouse PVRIG (mPVRIG) | Colon Cancer Renal Cell Carcinoma | |
Anti-TIGIT [125] | Anti-TIGIT (25 mg/kg), anti-PD-L1 (10 mg/kg), i.p. three times per week for 3 weeks | CT26 and EMT6 cells bearing BALB/c mouse model | Treatment of the combination of anti-TIGIT and anti-PD-L1 enhanced CD8+ T cell effector function which could be abrogated by the antibody of CD226. | Anti-PD-L1 Anti-CD226 | Colon Cancer Breast Cancer | |
Anti-TIGIT (clone 4B1 mIgG2) [126] | 200 μg i.p. per animal every other day for 5 doses (anti-TIGIT) or 3 doses (antI-PD-1) | GL261 cells bearing C57BL/6 J mouse model | Treatment with anti-PD-1 and anti-TIGIT improved survival, enhanced effector T cell function and reduced the infiltration of DCs and Tregs. | Anti-PD-1(4 H2) | Glioblastoma | |
Anti-TIGIT (Absolute Antibody; Clone 1B4; Mouse IgG1) [127] | 100 μg (anti-TIGIT) or 200 μg (anti-PD-1)/mouse i.p. every 2–3 days 100 μg (CD40 agonist) /mouse i.p. once every 4 weeks | Tumor bearing C57BL/6 J mouse model | Treatment of TIGIT/PD-1 co-blockade plus CD40 agonism showed significant anti-tumor function. | anti-PD-1 (BioXCell; Clone 29F.1A12; Rat IgG2a) CD40 agonist (BioXCell; Clone FGK4.5/FGK45; Rat IgG2a) | Pancreatic Cancer | |
Anti-TIGIT (#71340, 5 μg/mL, BPS Biosciences) [68] | Not mentioned | CD8+ T cells from human gastric cancer tissues | Treatment of anti-TIGIT or combination of anti-TIGIT and SOX enhanced the proliferation and IFN-γ production ability of CD8+ T cells. | S-1 plus oxaliplatin (SOX) | Gastric Cancer | |
|  | Anti-TIGIT therapy (clone IG9; BioX Cell, West Lebanon, NH, USA) [128] | Anti-TIGIT: 200 μg i.p. every 3 days for 4 injections Radiotherapy: 15Gy (1.65 Gy/min) | MC38, LLC, B16-F10 tumor cells bearing C57BL/6 mouse models | Administration of the anti-TIGIT enhanced the efficacy of radiotherapy by a CD8+ T cell-dependent manner. The combination treatment increased the infiltration of DCs. In addition CD103+ DCs were proved to promote the anti-tumor effects of combination therapy. | Radiotherapy | Colon Cancer Lung Cancer Melanoma |
|  | TIGIT-Fc-LIGHT (Bio X Cell, AdipoGen Life Sciences, and LSBio) [129] | 200 μg (TIGIT-Fc-LIGHT) or 100 μg (others) i.p. every 3 days for 3 times (mouse model), 0.1 mg/kg, 1 mg/kg, 10 mg/kg or 40 mg/kg i.v. every 7 days for 4 doses (cynomolgus macaques) | CT26/WT, CT26/AR, and B16-F10 tumor bearing BALB/c or C57BL/6 mouse model cynomolgus macaques | TIGIT-Fc-LIGHT exerted anti-tumor efficacy in mouse models regardless of the resistance to PD-1 blockade and showed tolerable toxicity in cynomolgus macaques. | Anti-PD-1 (clone RMP1–14), anti-PD-L1 (clone 10F.9G2), anti-TIGIT (clone 1G9), anti-LTbR (clone 4H8 WH2), TIGIT-Fc, Fc-LIGHT | Colorectal Cancer Melanoma |
|  | Anti-mouse TIGIT (4B1) [34] | 200 μg (anti-TIGIT) or 0.5 μg (IL15)/ 3.0 μg (IL15Ra) i.p. on day 0 and day 3, 250 mg (anti-CD226) on days − 1, 0 and 7 | B16-F10 or LWT1 tumor bearing C57BL/6 WT or Tigit−/− mouse model | The combination of IL15/IL15Ra and anti-TIGIT slowed down the tumor metastasis. | IL15/IL15Ra Complexes (R&D Systems) Anti-CD226 mAb (480.1) | Melanoma |
|  | VV- scFv- TIGITb [130] | 200 μg (anti-PD-1) i.p. every 2 days for 6–7 doses 200 μg (anti-LAG-3) i.p. every 4 days for 3 doses | CT26, MC38,4 T1, H22 bearing BALB/c or C57BL/6 mouse model | The intratumoral injection of VV-scFv-TIGIT elicited anti-tumor function, prolonged survival, increased T cells infiltration and activation of CD8+ T cells. Combination of anti-PD-1 or anti-LAG-3 enhanced the anti-tumor efficacy. | Anti-PD-1 (αPD1, Clone RMP1–14, Cat# BE0146, BioXCell) Anti-LAG3 (αLAG- 3, Clone C9B7W, Cat# BE0174, BioXCell) | Colorectal Carcinoma Breast Cancer Hepatocellular Carcinoma |
Hematological tumors | Anti-TIGIT (4B1, Bristol-Myers Squibb) [60] | 200 μg i.p. / twice per week for 4 weeks from week 4 | Vk12653, Vk12598 or 5TGM1 bearing C57BL/6 and TIGIT−/− mouse models | The application of an anti-TIGIT mAb decreased tumor burden, extended survival in the mouse models, and markedly amplified cytokine production along with degranulation of CD8+ T cells from MM patients. | Anti-PD-1 (RMP1–14; Bio X Cell) | MM |
|  | Anti-TIGIT (4B1, Bristol Myers Squibb) [61] | 100 μg i.p. / twice per week for 6 weeks | B6.WT mice transplanted with Vk12653 | Anti-TIGIT prolonged myeloma control after SCT | Not available | Myeloma |
|  | Anti-TIGIT (A15153G, BioLegend) [131] | Cells incubated with 50 μg/mL anti-TIGIT antibody in 96-well plates | TF-1, OCI-ALM3 and MV-4-11 cells | Single or combined with anti-CD39 or A2AR augmented the function of NK-92 cells or the lysis of AML cells | Anti-CD39 Anti-A2AR | AML |
|  | Anti-TIGIT (A15153G; BioLegend) [132] | Cells incubated with 50 μg/mL anti-TIGIT antibody in 96-well plates | AML associated TIGIT+ M2 or M1 macrophages | Anti-TIGIT mediated the phenotypic polarization transition from M2 to M1 and increased secretion of cytokines and chemokines associated with the M1 type and enhanced the phagocytosis induced by anti-CD47 | Anti-CD47 (CC2C6, BioLegend) | AML |