Phase I study of intratumoral administration of CV8102 in patients with advanced melanoma, squamous cell carcinoma of the skin, squamous cell carcinoma of the head and neck, or adenoid cystic carcinoma

Background
CV8102, a toll-like receptor 7/8 and RIG I agonist, has demonstrated antitumor immune responses in preclinical studies. We investigated intratumoral (IT) administration of CV8102 in patients with anti-programmed cell death protein-1 (PD-1) …

Blocking the CD39/CD73 pathway synergizes with anti-CD20 bispecific antibody in nodal B-cell lymphoma

Bispecific antibodies (BsAb) have emerged as a leading treatment modality in patients suffering from B-cell non-Hodgkin’s lymphoma (B-NHL). However, treatment failure is common and may potentially be attributed to pre-existing or emerging T-cell…

Comparative impact of tertiary lymphoid structures and tumor-infiltrating lymphocytes in cholangiocarcinoma

Background
Cholangiocarcinoma is a challenging malignancy with limited responses to conventional therapies, particularly immune checkpoint inhibitor therapy. Tumor-infiltrating lymphocytes (TILs) and tertiary lymphoid structures (TLSs) are key compone…

PD-1 cis-targeted IL-2v in combination with radiotherapy inhibits lung cancer growth and remodels the immune microenvironment

Background
More efficient therapeutic options for non-small cell lung cancer (NSCLC) are needed as the survival at 5 years of metastatic disease is near zero. In this regard, we used a preclinical model of metastatic lung adenocarcinoma (SV2-OVA) to a…

First-in-human, multicenter, open-label, phase I study of ATOR-1017 (evunzekibart), a 4-1BB antibody, in patients with advanced solid malignancies

Background
ATOR-1017 (evunzekibart) is a human agonistic immunoglobulin G4 antibody targeting the costimulatory receptor 4-1BB (CD137). ATOR-1017 activates T cells and natural killer cells in the tumor environment, leading to immune-mediated tumor cel…

Phase I study of BMS-986299, an NLRP3 agonist, as monotherapy and in combination with nivolumab and ipilimumab in patients with advanced solid tumors

Purpose
BMS-986299 is a first-in-class, NOD-, LRR-, and pyrin-domain containing-3 (NLRP3) inflammasome agonist enhancing adaptive immune and T-cell memory responses.

Materials and methods
This was a phase-I (NCT03444753) study that assessed the safet…

Safety and efficacy of PD-1 inhibitor (sintilimab) combined with transarterial chemoembolization as the initial treatment in patients with intermediate-stage hepatocellular carcinoma beyond up-to-seven criteria

Background
Numerous studies have demonstrated limited survival benefits of transarterial chemoembolization (TACE) alone in the treatment of intermediate-stage hepatocellular carcinoma (HCC) beyond up-to-seven criteria. The advent of immunotherapy, par…

First-in-human phase I trial of the bispecific CD47 inhibitor and CD40 agonist Fc-fusion protein, SL-172154 in patients with platinum-resistant ovarian cancer

Background
SL-172154 is a hexameric fusion protein adjoining the extracellular domain of SIRPα to the extracellular domain of CD40L via an inert IgG4-derived Fc domain. In preclinical studies, a murine equivalent SIRPα-Fc-CD40L fusion prot…

Cancer vaccines compensate for the insufficient induction of protective tumor-specific immunity of CD3 bispecific antibody therapy

Background
CD3 bispecific antibody (CD3 bsAb) therapy has become an established treatment modality for some cancer types and exploits endogenous T cells irrespective of their specificity. However, durable clinical responses are hampered by immune esca…

HDAC and MEK inhibition synergistically suppresses HOXC6 and enhances PD-1 blockade efficacy in BRAFV600E-mutant microsatellite stable colorectal cancer

Background
B-Raf proto-oncogene, serine/threonine kinase (BRAF)V600E-mutant microsatellite stable (MSS) colorectal cancer (CRC) constitutes a distinct CRC subgroup, traditionally perceived as minimally responsive to standard therapies. Recent clinical…

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