Phase I study of the safety and clinical activity of the interleukin-8 inhibitor AMY109 combined with atezolizumab in patients with advanced solid cancers

Background
Immunosuppressive conditions within the tumor microenvironment (TME) can allow tumors to evade the immune system, including by hampering programmed death ligand 1 (PD-L1) inhibitor activity. Interleukin (IL)-8 contributes to immunosuppressi…

Enhanced IL-15-mediated NK cell activation and proliferation by an ADAM17 function-blocking antibody involves CD16A, CD137, and accessory cells

Background
Natural killer (NK) cells are being extensively studied as a cell therapy for cancer. These cells are activated by recognition of ligands and antigens on tumor cells. Cytokine therapies, such as IL-15, are also broadly used to stimulate end…

Merkel cell carcinoma refractory to anti-PD(L)1: utility of adding ipilimumab for salvage therapy

Merkel cell carcinoma (MCC) incidence has risen to approximately 3,000 cases annually in the USA. Although anti-programmed cell death (ligand) 1 (PD-(L)1) agents are now the first-line treatment for advanced MCC, approximately 50% of such patients do …

rhIL-7-hyFc, a long-acting interleukin-7, improves efficacy of CAR-T cell therapy in solid tumors

Background
Chimeric antigen receptor T-cell (CAR-T) therapy has achieved remarkable remission in patients with B-cell malignancies. However, its efficacy in treating solid tumors remains limited. Here, we investigated a combination therapy approach us…

Impact of LAG-3/FGL1 pathway on immune evasive contexture and clinical outcomes in advanced urothelial carcinoma

Background
Anti-programmed death-1 (PD-1)/anti-PD-ligand-1 (PD-L1) pathway inhibition is a standard regimen for advanced urothelial carcinoma (UC); however, its limited efficacy has been reflected in reported medium response rates. This study explored…

Directing B7-H3 chimeric antigen receptor T cell homing through IL-8 induces potent antitumor activity against pediatric sarcoma

Background
Advances in pediatric oncology have occurred for some cancers; however, new therapies for sarcoma have been inadequate. Cellular immunotherapy using chimeric antigen receptor (CAR) T cells has shown dramatic benefits in leukemia, lymphoma, …

Peptide-based PET tracer targeting LAG-3 for evaluating the efficacy of immunotherapy in melanoma

Background
Lymphocyte activation gene 3 (LAG-3) is expressed on activated immune cells and has emerged as a promising target for immune checkpoints blockade. However, conflicting findings have been reported regarding the association between LAG-3 expr…

Subcutaneous checkpoint inhibition is equivalent to systemic delivery when combined with nelitolimod delivered via pressure-enabled drug delivery for depletion of intrahepatic myeloid-derived suppressor cells and control of liver metastases

Background
Toll-like receptor 9 (TLR9) agonists induce inflammatory responses that promote the killing of infectious micro-organisms, cancer cells and develop adaptive immune responses. Their ability as immunomodulators to enhance the activity of chec…

First-in-human dose escalation trial to evaluate the clinical safety and efficacy of an anti-MAGEA1 autologous TCR-transgenic T cell therapy in relapsed and refractory solid tumors

Rationale of the trial
Although the use of engineered T cells in cancer immunotherapy has greatly advanced the treatment of hematological malignancies, reaching meaningful clinical responses in the treatment of solid tumors is still challenging. We in…

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