We highlight trials where OVs prime checkpoint response (e.g., DNX-2401→pembrolizumab in recurrent glioblastoma) and where vector design (e.g., TK-deleted vaccinia, CG0070) or payloads (e.g., IFNβ, NIS) drive measurable benefit. We conclude with actionable priorities, patient selection by IFN-pathway competence, receptor-tropism panels, and rational OV-ICI sequencing, to accelerate durable responses.

Here, we describe a case of a woman with stage IIIC melanoma undergoing intralesional talimogene laherparepvec (T-VEC) therapy who developed a spreading erythematous rash on her left leg, accompanied by fatigue and leg swelling. Skin biopsy revealed recurrent melanoma, with SOX10 and Melan-A positivity, and imaging showed features concerning for multifocal disease recurrence in the left popliteal fossa. This case highlights an unusual presentation of melanoma recurrence and underscores the importance of biopsy in -evaluating new skin findings in patients with a history of melanoma.

Nadofaragene firadenovec, a recombinant adenovirus delivering interferon alpha-2b (IFNα2b), is the first FDA-approved gene therapy for BCG-unresponsive NMIBC with carcinoma in situ (CIS)...Cretostimogene grenadenorepvec (CG0070), an oncolytic vector, demonstrated a 47% 6-month CR rate in a phase II study (NCT02365818). Detalimogene voraplasmid (EG-70), a nonviral gene therapy, demonstrated a 47% 6-month CR in a phase I/II study (NCT04752722). Future advances are likely to focus on patient selection, novel vectors, and combination strategies to improve treatment outcomes. Gene therapy represents a significant addition to the bladder cancer treatment landscape by offering bladder-sparing alternatives where conventional therapies are limited.

Compared with T-VEC, the classical therapeutic agent that only expresses GM-CSF, which was approved in 2015, most new oncolytic virus designs include diverse gene constructs to reduce toxic effects, enhance multiple antitumor immunity, avoid immune clearance, or enhance tumor targeting...Finally, we explored the feasibility of the intravenous application of oncolytic viruses and their future development directions. We believe that the diversified treatment design of oncolytic viruses will bring more surprises to the immunotherapy of refractory tumors.

P2, N=43, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Nov 2025 --> Nov 2026

Post-transplant recovery was marked by poor initial engraftment, requiring platelet transfusions and biweekly filgrastim...Despite hematologic recovery, qPCR consistently revealed persistent BCR::ABL1 p190 expression, indicating residual disease. This case underscores the challenge of eradicating leukemic stem cells (LSCs) in high-risk AML and supports the integration of next-generation flow cytometry for enhanced MRD and LSC assessment post-transplant.

P=N/A, N=187, Active, not recruiting, Amgen | Recruiting --> Active, not recruiting | N=300 --> 187 | Trial completion date: Jan 2038 --> Jan 2026 | Trial primary completion date: Jan 2038 --> Jan 2026

P1, N=10, Not yet recruiting, Johns Hopkins University | Initiation date: Nov 2025 --> Feb 2026

P1, N=10, Active, not recruiting, City of Hope Medical Center | Trial completion date: Oct 2025 --> Sep 2026 | Trial primary completion date: Oct 2025 --> Sep 2026

P2, N=150, Recruiting, Masonic Cancer Center, University of Minnesota | Trial completion date: Apr 2026 --> Apr 2027 | Trial primary completion date: Sep 2025 --> Sep 2026

P2, N=62, Recruiting, New Approaches to Neuroblastoma Therapy Consortium | Active, not recruiting --> Recruiting

P2, N=38, Recruiting, Northside Hospital, Inc. | Trial completion date: Sep 2025 --> Sep 2026 | Trial primary completion date: Sep 2025 --> Sep 2026