Oncolitici

Oncolitici, or oncolytic agents, are therapeutic modalities designed to selectively infect, replicate in, and lyse cancer cells while minimizing damage to normal tissues. They encompass a range of biologic agents, most notably oncolytic viruses, but also include oncolytic bacteria and other engineered biological constructs. The overarching goal is to achieve direct tumor cell destruction and to stimulate anti-tumor immune responses that help control disease.

The principal mechanism of action combines several effects. First, the agents preferentially replicate in cancer cells due to defects in antiviral responses or tumor-specific receptors, leading to lysis of malignant cells. Second, the destruction of tumor cells releases tumor-associated antigens and danger signals that recruit and activate dendritic cells and other components of the immune system. Third, the local inflammatory milieu can enhance systemic anti-tumor immunity and may improve the efficacy of other therapies, including immune checkpoint inhibitors. Some oncolytic agents are genetically modified to express immune-stimulating factors, such as cytokines, to boost these responses.

Among oncolytic viruses, the most clinically established example is talimogene laherparepvec (T-VEC), a genetically modified herpes simplex virus expressing GM-CSF, approved for melanoma in several regions and used as intratumoral injections. Other viruses (adenoviruses, vaccinia, reovirus, HSV derivatives) are under investigation in various cancers, often in combination with checkpoint blockade or other standard therapies. Oncolytic bacteria, such as engineered Clostridium or Salmonella strains, have also been explored, particularly for solid tumors with hypoxic regions.

Challenges include ensuring selective tumor targeting, managing inflammatory side effects, overcoming pre-existing antiviral immunity, and determining optimal delivery routes and combination strategies. Ongoing research aims to expand indications, improve efficacy, and integrate oncolitics into multimodal cancer therapy.