indoximod (NLG8189)

To address this, a multifunctional nanoparticle, TPI@RPB, was constructed with RGD-PEG-BSA as the carrier for tumor-targeted delivery, while co-loading the self-synthesized endoplasmic reticulum (ER) target photosensitizer TSE-Ppa and Indoleamine 2,3-dioxygenase 1 (IDO-1) inhibitor 1-MT...In vivo, TPI@RPB not only demonstrates active tumor targeting but also significant antitumor efficacy with a favorable safety profile; specifically, tumor weight reduced to 13.70%, intratumoral CD8+ T-cell infiltration increased 1.92-fold, Treg cells decreased to 51.7%, and splenic effector-memory T cells increased 4.70-fold of control, with no observable systemic toxicity. These results suggest that ER-targeted PDT combined with IDO-1 blockade effectively remodels the tumor microenvironment and elicits durable antitumor immunity in TNBC.

Importantly, the accumulation of myeloid-derived suppressor cells (MDSCs), a key driver of tumor progression and metastasis, decreased in the primary tumor, metastatic liver, and lung of mice treated with indoximod and melatonin combination. Our findings revealed that melatonin enhances the immunotherapeutic efficacy of indoximod in TNBC.

Here, we design and construct an in situ injectable therapeutic hydrogel encapsulating 1-methyl-d-tryptophan (1-d-MT), a small-molecule competitive inhibitor of indoleamine 2,3-dioxygenase, and meloxicam, a selective inhibitor of cyclooxygenase-2 (Ge1MT/Mel hydrogel) to prevent postoperative tumor metastasis and relapse. Importantly, the Ge1MT/Mel hydrogel markedly stimulates a potent antitumor immune response in the cancer lesion microenvironment, increasing antitumor immune cells including CD8+ T cells, as well as elevating antitumor cytokines such as interferon-γ. Overall, combination immunotherapy via the Ge1MT/Mel hydrogel after surgery represents a promising strategy to minimize residual tumor burden and reduce recurrence risk following tumor resection.

This effect was suppressed after 1-methyltryptophan (1-MT) treatment, indicating that it is IDO-dependent...Experimental evidence has revealed that mouse CD4+ T cells undergo apoptosis via IDO following T. spiralis infection, and that weakened proliferation leads to an imbalance in mouse immune function, facilitating the smooth survival of T. spiralis and evasion of host immune attack. These findings provide new directions and insights for studying the immune escape mechanism of T. spiralis and for the prevention and treatment of T. spiralis infection.

Here, an iridium (Ir)-based nanozyme (IIN) was constructed through coordination-driven co-assembly using photosensitizer indocyanine green (ICG), Ir, and indoleamine 2,3-dioxygenase (IDO) inhibitor NLG8189...Furthermore, it could suppress distant tumor progression by triggering the immune response, especially under photothermal irradiation, which was accompanied by increased DC maturation, M1 macrophage polarization, and T cell infiltration in tumor tissue. This study proposed a promising strategy for effective Ir-based nanozyme in tumor immunotherapy.

In this study, we produced near-infrared (NIR)-induced multi-shell upconversion nanoparticle (MUN)-based therapeutic nanocarriers co-loaded with chlorin e6 (Ce6) and indoximod (IND) (FMUN3-Ce6/IND) to combine tumor-targeted photodynamic therapy (PDT) with immunotherapy...Furthermore, the synergistic antitumor efficacy of FMUN3-Ce6/IND combining PDT and immunotherapy under in vivo conditions is demonstrated. These results suggest that multi-shell FMUN-based nanocarriers offer a promising platform for synergistic combination therapy, addressing the limitations of monotherapy with IDO inhibitors and overcoming the restricted tissue penetration and low ROS generation associated with conventional PDT.

Four novel Ir(III)/Re(I)-1-methyl-D-tryptophan conjugates (Ir-MT-1-2 and Re-MT-1-2) were designed and synthesized for the first time, among which 1-methyl-D-tryptophan (1-MT) is an indoleamine 2,3-dioxygenase (IDO) inhibitor...Mechanistic investigations revealed that these complexes selectively localized to mitochondria, inducing mitochondrial membrane potential (MMP) depolarization, elevating intracellular reactive oxygen species (ROS) levels, activating mitochondrial apoptotic pathways, and simultaneously inducing the cleavage of pyroptosis marker (GSDME) to cause pyroptosis. These results demonstrate the potential of combing transition metals with IDO inhibitors for cancer treatment.

In this study, a formulation of DOX/IND-loaded liposomes camouflaged with ovarian cancer cell membranes is successfully developed, and their stable physicochemical properties are confirmed. As an effective nanodrug delivery system, DOX/IND@cmLPs exhibited enhanced tumor-targeting and immune-mediated anticancer activity both in vitro and in vivo, indicating their potential as a platform for future combined chemotherapy and immunotherapy.

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.