Programmable immunotherapy in precision oncology: integrating oncolytic viruses and neoantigen vaccines

Camelia Dascalu ^{1, 2 *}, Miruna Furtuna ², Constantin Roman ², Georgiana Gotcu ², Bogdan-Ionel Tamba ^{1, 2}

¹ Department of Pharmacology, Clinical Pharmacology and Algesiology, Grigore T. Popa University of Medicine and Pharmacy, Iasi, Romania
² Prof. Ostin C. Mungiu Advanced Research and Development Center for Experimental Medicine – CEMEX, Grigore T. Popa University of Medicine and Pharmacy, Iasi, Romania
* Correspondence to: Camelia Dascalu, Prof. Ostin C. Mungiu Advanced Research and Development Center for Experimental Medicine – CEMEX, Grigore T. Popa University of Medicine and Pharmacy, 16 Universitatii Str., 700115, Iasi, Romania. E-mail: camelia-enascut@email.umfiasi.ro

Abstract

Oncolytic viruses and therapeutic cancer vaccines are two immunotherapy platforms whose trajectories increasingly intersect. Both aim not only to destroy malignant cells directly, but also to train the patient’s immune system to mount long-lasting antitumor responses. Unlike conventional cytotoxic agents, whose effects follow relatively linear pharmacokinetic–pharmacodynamic principles, these biological platforms work by amplifying immune activity. Oncolytic virotherapy has moved far beyond the early observation that certain viruses preferentially replicate in tumor cells. It is now a deliberately engineered approach—programmable by design—that pairs direct viral lysis of cancer cells with an in situ vaccination effect generated by the release of tumor antigens. In parallel, therapeutic cancer vaccines, particularly those built on neoantigens, provide highly precise immune targeting by focusing on tumor-specific epitopes created by somatic mutations. By doing so, they circumvent the constraints of central immune tolerance and elicit more potent, tumor-restricted T-cell responses. Despite their strong mechanistic foundations and promising results in preclinical models, both oncolytic viruses and therapeutic cancer vaccines have shown only modest clinical efficacy when used as monotherapies. This gap between biological potential and clinical performance is shaped by several well-recognized barriers: the immunosuppressive nature of the tumor microenvironment, the heterogeneous expression of tumor antigens, patient-specific variability driven by immune status, and the substantial regulatory complexity associated with these evolving biologic platforms. Growing evidence now suggests that these limitations may be overcome by integrating oncolytic virotherapy with therapeutic or neoantigen-based vaccines and, increasingly, with immune checkpoint inhibitors. Such rational combinations appear to enhance immune priming, broaden antigenic targeting, and mitigate both primary and acquired forms of immune resistance. From a translational clinical pharmacology perspective, these platforms challenge the traditional assumptions that link dose, exposure, and therapeutic effect. Their activity is shaped largely by immune amplification rather than predictable pharmacokinetic behavior, making patient selection and response evaluation heavily dependent on immune-guided biomarkers. This review synthesizes the fundamental platform biology underlying oncolytic viruses and therapeutic cancer vaccines, highlights how their integration can advance precision oncology, and examines the key clinical pharmacology and regulatory hurdles that continue to limit their widespread clinical adoption.