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Delivery of Immune Checkpoint Inhibitors Using Nanoparticles
Published in Hala Gali-Muhtasib, Racha Chouaib, Nanoparticle Drug Delivery Systems for Cancer Treatment, 2020
Abdullah Shaito, Houssein Hajj Hassan
So far, more than twenty different checkpoint molecule pairs have been discovered, other than CTLA-4 and PD-1, including LAG-3/MHCII, TIGIT/CD155, and TIM3/Gal-9, which are expressed, with varying levels, not only on T-cells but by other immune cells as well [45–47].
Investigational drugs for recurrent or primary advanced metastatic cervical cancer: what is in the clinical development pipeline?
Published in Expert Opinion on Investigational Drugs, 2023
Ignace Vergote, Isabelle Ray-Coquard, Domenica Lorusso, Ana Oaknin, David Cibula, Toon Van Gorp
Several types of lymphocytes express the inhibitory receptor, TIGIT, including TILs [51]. TIGIT is an inhibitory receptor expressed on activated CD4+, CD8 + T cells, natural killer cells, regulatory T cells and follicular T helper cells and blocking of TIGIT restores the ability of CD8 + T-cells to produce cytokines [52]. The ongoing KEYVIBE-001 trial is investigating two doses (200 or 700 mg every 3 weeks) of the anti-TIGIT therapy, vibostolimab, in combination with pembrolizumab in PD-L1 inhibitor-naïve advanced or metastatic CC. Recent results report that antitumor activity was comparable between doses and efficacy was seen irrespective of PD-L1 status [81]. As a result of this success, the ongoing KEYVIBE-005 trial (NCT05007106) is evaluating this combination in CC irrespective of PD-L1 tumor status at the recommended dose of 200 mg every 3 weeks. Investigation into the combination of anti-PD1 antibody, tislelizumab, with or without another anti-TIGIT antibody, and ociperlimab, is also currently ongoing (NCT04693234) in patients with previously treated R/M CC.
A patent review of pharmaceutical and therapeutic applications of oxadiazole derivatives for the treatment of chronic diseases (2013–2021)
Published in Expert Opinion on Therapeutic Patents, 2022
Abbas Hassan, Abid Hussain Khan, Faiza Saleem, Haseen Ahmad, Khalid Mohammed Khan
Nair reported amino acid derivatives of 1,2,4- and 1,3,4-oxadiazole as capable of modulating the T cell immunoreceptor with Ig and ITIM domains (TIGIT) signaling pathways [23]. These compounds are therefore helpful in the treatment of disorders associated with TIGIT signaling pathways. To treat diseases by controlling the immune response to a pathogen or tumor cell is the main purpose of immunotherapy, which may induce/enhance and inhibit/reduce specific immune responses. TIGIT is a co-inhibitory receptor protein that potentially plays a role in potentiating immune-related diseases such as cancer. There exists a need to develop potent therapeutic agents that show better selective inhibition of TIGIT signaling pathways. In the bioassay, the rescue of the mouse CD8 + T-cell proliferation in the presence of recombinant mPVR was determined. For the determination of the increased proliferation of CD8 + T cells, a recombinant mouse anti-TIGIT antibody was used as the positive control. Percent CD8 + T cell proliferation was analyzed by measuring IL-2 levels using an IL-2 ELISA kit, and percent rescue of CD8+ T cell by test compound was estimated. Compounds 7, 8, and 9 demonstrated 102%, 98%, and 72% rescue of CD8+ T cell at 100 nM concentration, respectively (Figure 4).
Upregulation of TIGIT and PD-1 in Colorectal Cancer with Mismatch-repair Deficiency
Published in Immunological Investigations, 2021
Xuebing Zhou, Xiaoling Ding, Hai Li, Chun Yang, Zhanbing Ma, Guangxian Xu, Shaoqi Yang, Dong Zhang, Xiaoliang Xie, Lei Xin, Xiaoli Luo
CRC is a cancer with a poor prognosis. dMMR is common in CRC and is associated with an even poorer prognosis (Clark et al. 2004). In addition, the dMMR phenotype has therapeutic implications (O’Kane et al. 2017). Lynch Syndrome is caused by mutations in the genes involved mismatch repair and is the cause of 2%-12% of CRCs (Moreira et al. 2012; Mork et al. 2015; O’Kane et al. 2017). Despite great efforts to develop effective anti-cancer treatments, there has been little progress in the prognosis of CRC during the past decades. TIGIT regulates the immune response (Stanietsky et al. 2009; Stengel et al. 2012; Yu et al. 2009). PD-1 is involved in the immune escape mechanisms of solid tumors (Ahmadzadeh et al. 2009; Blank and Mackensen 2007; Grosso et al. 2007; Sakuishi et al. 2010). Their combined role in colorectal cancer is unknown. Therefore, this study aimed to examine the role of TIGIT and PD-1 in patients with CRC and on the function of activated T cells. The results strongly suggest that TIGIT and PD-1 are upregulated in CRC with dMMR tissues. TIGIT and PD-1 expression was associated with the TNM stage and DFS.