Identification of anti-TIM-3 based checkpoint inhibitor combinations with activity in immunotherapy refractory melanoma models

Background
A significant percentage of melanomas are refractory to immune checkpoint inhibitor (ICI) monotherapies and combinations. As there are currently no effective second-line therapies available for ICI-resistant patients, we sought to identify …

Biomineralized engineered Lactococcus lactis-based in situ vaccination enhances antitumor immunity via sequential activation of chemo-immunotherapy

Background
Combining chemotherapy with immunotherapy is a promising strategy to enhance in situ immunity by increasing antigen exposure and inflammation in the tumor microenvironment (TME). However, the inconvenience of separate administration and the…

Autoimmune origin for immune checkpoint inhibitor-diabetes revealed by deep immune phenotyping of the pancreas

Immune checkpoint inhibitor-diabetes (CPI-D) is an acute and non-resolving immune-related adverse event (irAE) initiated primarily by disrupting the programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) axis with monoclonal antibodies. A major l…

Immunotherapy versus lenvatinib in hepatocellular carcinoma: the need for granular data and prospective validation

Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related mortality worldwide, with systemic therapies constituting the cornerstone of treatment for advanced-stage disease. While lenvatinib has been a widely used first-line agent, the a…

Phase II study of retifanlimab in patients with recurrent locally advanced or metastatic Merkel cell carcinoma (POD1UM-201)

Background
POD1UM-201, an open-label, single-arm, phase II multiregional study, evaluated efficacy and tolerability of retifanlimab, a humanized monoclonal antibody targeting programmed cell death protein-1 (PD-1) in chemotherapy-naive patients with r…

Risk of disease progression after discontinuing immunotherapy in 105 patients with Merkel cell carcinoma who responded to PD-1 pathway blockade

Background
Immune checkpoint inhibitors (ICIs) are the preferred systemic therapy for most patients with advanced Merkel cell carcinoma (MCC). However, the optimal duration of treatment for patients responding to ICI is unclear. Emerging data from ret…

Temporal optimization of CD25-biased IL-2 agonists and immune checkpoint blockade leads to synergistic anticancer activity despite robust regulatory T cell expansion

Background
Interleukin-2 (IL-2) immunotherapy can induce durable tumor remissions, but its clinical performance has been limited by significant drawbacks such as short serum half-life and high toxicity. Administration of IL-2 in complex with certain a…

Universal off-the-shelf combination immunotherapy using oncolytic viruses to redirect T cell engagers to target solid tumors

Background
Bispecific T cell engager (BiTE), such as blinatumomab, has demonstrated significant clinical success in treating hematological malignancies like B cell acute lymphoblastic leukemia and non-Hodgkin’s lymphoma. However, the application of Bi…

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