Intratumoral oncolytic virus OH2 injection in patients with locally advanced or metastatic sarcoma: a phase 1/2 trial

Background
Intratumoral oncolytic herpes simplex virus 2-GM CSF (OH2) injection has shown safety and antitumor efficacy in patients with solid tumors. Here, we examined the safety and efficacy of OH2 as a single agent or in combination with HX008, an …

Targeting Siglec-E facilitates tumor vaccine-induced antitumor immunity in renal carcinoma

Background
Siglec-E is an immune checkpoint inhibitory molecule. Expression of Siglec-E on the immune cells has been shown to promote tumor regression. This study aimed to develop an adenovirus (Ad) vaccine targeting Siglec-E and carbonic anhydrase IX…

Engineered GM-CSF polarizes protumorigenic tumor-associated macrophages to an antitumorigenic phenotype and potently synergizes with IL-12 immunotherapy

Background
The use of immune checkpoint inhibitors (CPIs) has become a dominant regimen in modern cancer therapy, however immune resistance induced by tumor-associated macrophages (TAMs) with immune suppressive and evasion properties limits responses….

Oncolytic vaccinia virus armed with anti-CD47 nanobody elicit potent antitumor effects on multiple tumor models via enhancing innate and adoptive immunity

Objective
Targeting CD47 for cancer immunotherapy has been studied in many clinical trials for the treatment of patients with advanced tumors. However, this therapeutic approach is often hampered by on-target side effects, physical barriers, and immun…

Additional expression of T-cell engager in clinically tested oncolytic adeno-immunotherapy redirects tumor-infiltrated, irrelevant T cells against cancer cells to enhance antitumor immunity

Background
Oncolytic adenoviruses (OAds) are the most clinically tested viral vectors for solid tumors. However, most clinically tested “Armed” OAds show limited antitumor effects in patients with various solid tumors even with increased dosages and m…

Mitochondrial metabolic reprogramming of macrophages and T cells enhances CD47 antibody-engineered oncolytic virus antitumor immunity

Background
Although immunotherapy can reinvigorate immune cells to clear tumors, the response rates are poor in some patients. Here, CD47 antibody-engineered oncolytic viruses (oAd-αCD47) were employed to lyse tumors and activate immunity. The o…

Durable antitumor response via an oncolytic virus encoding decoy-resistant IL-18

Background
Interleukin-18 (IL-18), or interferon (IFN)–inducing factor, potentiates T helper 1 and natural killer cell activation as well as CD8+ T-cell proliferation. Recombinant IL-18 has displayed limited clinical efficacy in part due to the expre…

Intratumoral STING agonist reverses immune evasion in PD-(L)1-refractory Merkel cell carcinoma: mechanistic insights from detailed biomarker analyses

Background
Antibodies blocking programmed death (PD)-1 or its ligand (PD-L1) have revolutionized cancer care, but many patients do not experience durable benefits. Novel treatments to stimulate antitumor immunity are needed in the PD-(L)1 refractory s…

Nanoparticles targeting immune checkpoint protein VISTA induce potent antitumor immunity

Background
Immune checkpoint protein V-domain immunoglobulin suppressor of T cell activation (VISTA) controls antitumor immunity and is a valuable target for cancer immunotherapy. Previous mechanistic studies have indicated that VISTA impairs the toll…

Adenovirus vaccine targeting kinases induces potent antitumor immunity in solid tumors

Background
Targeting kinases presents a potential strategy for treating solid tumors; however, the therapeutic potential of vaccines targeting kinases remains uncertain.

Methods
Adenovirus (Ad) vaccines encoding Aurora kinase A (AURKA) or cyclin-depe…

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