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.

IO102-IO103 plus pembrolizumab prolonged progression-free survival compared with pembrolizumab alone in patients with advanced melanoma in the first-line setting; however, statistical significance was missed for the primary endpoint. The combination was well tolerated with no added significant systemic toxicity. These data show the potential benefit of this combination in untreated advanced melanoma.

P2, N=63, Completed, IO Biotech | Active, not recruiting --> Completed | Trial completion date: Nov 2024 --> Feb 2026 | Trial primary completion date: Jan 2024 --> Nov 2025

Herein, by using a one-pot approach, we developed a carrier-free nanoreshaper (QN NP) through coordinating manganese ions (Mn2+) with quercetin (Qc) and the indoleamine 2,3-dioxygenase 1 inhibitor NLG919 to lift these restrictions...Furthermore, combining QN NPs with an anti-PD-L1 antibody generated robust synergistic activity, leading to cooperative suppression of both primary tumor growth and pulmonary metastases. This carrier-free nanoreshaping strategy overcomes the dual challenges of stromal fibrosis and immune evasion, providing a promising paradigm for developing combined immunotherapies based on physical barrier disruption and microenvironment reprogramming.

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.

P2, N=30, Recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | N=15 --> 30

In addition, the immunosuppressive microenvironment exacerbated by postoperative hypoxia is degraded via the cooperation of NLG919, which blocks the IDO-1 signaling pathway and CaCO3, which consumes lactic acid. Based on these improvements, well-designed MOFs effectively inhibit bilateral tumor growth/metastasis and offer a successful paradigm for improving the overall prognosis of HIFU.

An ongoing first-in-human (FIH) phase 1/2 clinical trial (NCT05533697) will evaluate the safety and antitumor activity of mRNA-4359 when administered alone and in combination with the anti-programmed death-1 agent pembrolizumab in participants with advanced solid tumors. Finally, the IS/ID modeling analysis determined that a 100 μg dose of mRNA-4359 would be the most appropriate starting dose for FIH trials. The described approach represents a unique application of IS/ID modeling to determine a therapeutically relevant FIH starting dose in the absence of supporting preclinical animal data.

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.