indoximod (NLG8189)

Among these, medications like Indoximod, Epacadostat, and Navoximod have shown promise in influencing the immune system and slowing tumor progression, while dual inhibitors like HTI-1090 try to address broader metabolic connections. The use of IDO/TDO inhibitors with conventional anticancer medications demonstrates their potential to reshape cancer treatment paradigms, contingent on further research to optimize efficacy and safety. Clinical Trial Registration: https://clinicaltrials.gov/study/NCT03844438.

To address these challenges, we developed a novel photosensitizer (PS), TTVBO-1MT, by conjugating the indoleamine 2,3-dioxygenase 1 (IDO1) inhibitor 1-methyl-d-tryptophan (1-MT) to the aggregation-induced emission (AIE) PS TTVBO via a glutathione (GSH)-responsive linker...This combined effect promoted T-cell infiltration and triggered a systemic antitumor immune response. Overall, the results suggest that TTVBO-1MT enables autophagy-assisted immuno-photodynamic modulation of the tumor microenvironment (TME), offering significant therapeutic potential.

However, PAF levels remained elevated despite treatment, indicating limited efficacy in PAF-associated pathways. Indoximod exhibited anti-inflammatory effects in this acute colitis model, likely by downregulating key proinflammatory mediators.

In this study, a multi-bioactive nanocomposite consisting of hyaluronic acid-block-poly(1-methyl-d-tryptophan-co-l-glutamic acid) (HA-PMTG) and tetracarboxyl porphyrin-trivalent Fe(III) metal-organic framework (MOFTCPP-Fe) was developed for enhanced cascading PDIT...Furthermore, treatment with HA-PMTG@MOFTCPP-Fe on the primary tumor inhibited distant tumor growth through a bystander effect and prevented tumor recurrence by activating immune memory. Thus, the multi-bioactive HA-PMTG@MOFTCPP-Fe offers an effective cascading strategy to enhance the PDIT of cancer.

Also, by the elevated secretion of IL-12 cytokine, T cells release high levels of IFNγ, which is a central role in IL-12-mediated immunotherapy. This co-delivery system presents a promising strategy to overcome the limitations of single IL-12-mediated therapy by simultaneously promoting antitumor immune responses and inhibiting immunosuppressive mechanisms, thereby enhancing the overall efficacy of cancer immunotherapy.

A diblock polymer polyprodrug was synthesized with the IDO inhibitor 1-methyl-tryptophan (1-MT) linked by thioketal bonds and the photosensitizer 5,10,15,20-tetraphenylporphyrin (TPP) in the hydrophobic block as well as endoplasmic reticulum (ER) targeting group (4-methylphenyl) sulfonamide in the hydrophilic block...Finally, SR@ET-PMT can attain an 88% suppression rate of solid tumors due to the potent immunotherapeutic efficacy. The photoactivatable immunomodulator polyprodrugs are successfully prepared to simultaneously deliver STING agonists and IDO inhibitors, which represent a promising nanomedicine for the spatiotemporal activation of synergistic antitumor immunity.

Tumor microenvironment (TME) immune profiling revealed that CDs-IND reduced IDO expression and recruited NK, NKT, and T cells. This study underscores the potential of combining the inherent pharmacological properties of CDs with indoximod-mediated immunotherapy, offering a promising strategy for precision breast cancer treatment.

Combining indoximod and oHSV significantly inhibited tumor growth, and induced antigen specific CD8+ T cell activation. These results suggest that inhibition of the IDO pathway could significantly block feedback immunosuppression during oncolytic virotherapy of glioblastoma.

GC cell lines (MFC and NCI-N87) and PBMC cells were co-cultured and IDO inhibitor 1-methyl-tryptophan (1-MT) was added...IDO may suppress the proliferation of T lymphocyte through inhibiting the PI3K/Akt/mTOR signaling pathway. This provides new evidence for the potential of exploiting IDO inhibitors for GC treatment.

In this study, TME-responsive nanoparticles (HMP1G NPs) loaded with 1-methyltryptophan (1-MT; an indoleamine 2,3-dioxygenase 1 [IDO1] inhibitor,) and S-nitrosoglutathione (GSNO; a nitric oxide donor) is developed to enhance the therapeutic efficacy of 1-MT-mediated ICB...In a murine breast cancer model, treatment with HMP1G NPs elicited effective antitumor immunity and enhanced survival outcomes. This study highlights a novel nano-platform that simultaneously improves metabolism and enhances ICB efficacy to achieve a new and efficient antitumor strategy.

The PCMZ NPs, possessing good photothermal conversion capabilities due to join of PDA, effectively overcome two main challenges in immunotherapy: insufficient stimulation of the immune response and evasion of the immune system. This provides a robust platform against invasive cancer and recurrent tumors.

After intratumoral injection of PCur/IND@Gel, significant apoptosis in 4T1 tumors was induced, dendritic cells in lymph nodes were highly activated, potent CD8+ and CD4+ antitumor immune responses were elicited and regulative T cells in tumors were significantly reduced, which notably inhibited the tumor growth and prolonged the survive time of 4T1 tumor-bearing mice. Therefore, this injectable nanocomposite hydrogel is a promising drug co-delivery platform for chemo-photothermal-immunotherapy of breast tumors.