In situ APMV-4 vaccination primes systemic response to subtherapeutic dosing of aCTLA-4 in colorectal carcinoma

Background
Colorectal carcinoma (CRC) is frequently typified by chronic inflammation and high levels of immunosuppression that render it resistant to immunotherapy. The multimodal immunostimulatory mechanisms of oncolytic virotherapy make it an attrac…

IL-23-engineered oncolytic vaccinia virus enhances pancreatic cancer control through inflammasome-driven Th17-skewed CD4+ T-cell responses

Background
Oncolytic viruses represent a promising immunotherapeutic strategy for converting pancreatic and other immunologically cold tumors. While their ability to stimulate innate immune signaling and promote antitumor immunity is established, mech…

Prolonged survival after systemic immune reactivation by aglatimagene besadenovec plus valacyclovir in immune checkpoint inhibitor-refractory non-small cell lung cancer

Background
Patients with advanced non-small cell lung cancer who progress on immune checkpoint inhibitors (ICIs) face limited options and poor survival. Aglatimagene besadenovec (CAN-2409), a replication-defective adenoviral vector encoding herpes sim…

Intravenously deliverable oncolytic virus VET3-TGI favorably alters the tumor microenvironment

Background
Oncolytic viruses have pledged to combat cancer by causing immunogenic cell death of cancerous cells while priming cancer-specific immune responses. These outcomes have proven elusive in the clinic. Current-generation vectors rarely reach e…

Anti-CTLA-4 antibody potentiates the antitumor effect of armed oncolytic virus OVM18 via enhancing intratumoral IL-18R1+CD8+ T cells

Background
Oncolytic virus M1 encoding a mutant IL-18 decoy (OVM18) represents a novel virotherapy that integrates selective oncolysis with localized activation of the IL-18 pathway. However, the heterogeneity of therapeutic responses suggests that ho…

Mechanistic modeling of tumor immune microenvironment reveals strategies to enhance antibody-drug conjugates efficacy

Background
Antibody-drug conjugates (ADCs) and bispecific antibodies represent a rapidly advancing frontier in oncology, yet the abnormal tumor microenvironment (TME) hinders their delivery and reduces efficacy. Emerging immunomodulatory ADCs (IM-ADCs…

Immune-cytokine signature predicts survival in patients with advanced melanoma treated with oncolytic adenovirus TILT-123 and chemotherapy and IL-2-free adoptive TIL therapy

Background
Metastatic melanoma resistant to immune checkpoint inhibitors remains difficult to treat, and while adoptive tumor-infiltrating lymphocyte (TIL) therapy has shown durable responses, its reliance on lymphodepleting chemotherapy and high-dose…

Focused ultrasound thermal ablation and CD40 agonism reprograms breast tumor immunity to drive regression and memory

Background
Focused ultrasound thermal ablation (T-FUS) is a clinically accessible, non-invasive modality capable of inducing rapid tumor cytoreduction while mobilizing early immunologic danger signals. However, its capacity to synergize with potent co…

CXCR2-mediated metabolic interaction between prostate cancer cells and the immunosuppressive tumor microenvironment

Background
Neuroendocrine prostate cancer (NEPC) is characterized by strong immune evasion and profound metabolic reprogramming. A high regulatory T cell (Treg)/CD8+ T cell ratio and an increased proportion of M2/M1 tumor-associated macrophages (TAMs)…

FLT3L-secreting cDC1 in situ vaccination enhances antitumor immunity and synergizes with PD-1 blockade in murine non-small cell lung cancer

Background
Non-small cell lung cancer (NSCLC) frequently evades immune surveillance through defective antigen presentation and a suppressive tumor microenvironment (TME), limiting the efficacy of immune checkpoint blockade (ICB). Conventional type 1 d…

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