T-VEC virotherapy yielded complete responses in injected lesions in 46% of patients in a phase I trial.

  • Major Finding: T-VEC virotherapy yielded complete responses in injected lesions in 46% of patients in a phase I trial.

  • Concept: Surprisingly, intralesional injection of T-VEC induced immune responses even in noninjected lesions.

  • Impact: This trial reveals that a virotherapy can elicit immune responses in a cell type–nonspecific manner.

Oncolytic virotherapies are genetically modified viruses that are injected into target lesions to trigger an antitumor immune response. One such virotherapy, a genetically engineered herpes simplex type 1 virus named talimogene laherparepvec (T-VEC), is approved for the treatment of cutaneous melanoma metastases and is being investigated in other malignancies. Recently, Ramelyte, Tastanova, Balázs, and colleagues conducted a phase I trial to determine if T-VEC could be used to treat primary cutaneous B cell lymphoma (pCBCL), a type of non-Hodgkin lymphoma that presents primarily on the skin. In this study, 13 patients received intralesional T-VEC injections into some, but not all, cutaneous lymphoma lesions. The safety and tolerability profile was as expected for T-VEC, with the most common treatment-emergent adverse event being flu-like symptoms. Complete responses in the injected lesions were detected in six patients (46.2%), five patients (38.4%) exhibited partial responses in the injected lesions, and two patients (15.4%) had progressive disease. Surprisingly, single-cell RNA sequencing analyses of 35 longitudinally collected fine-needle aspirates of T-VEC–injected or noninjected lesions showed that the number of B cells decreased whereas the number of natural killer cells, dendritic cells, monocytes, and CD4+ and CD8+ T-cells increased in both T-VEC-injected and noninjected lesions. This finding provides evidence that T-VEC's antitumor activity occurs by a general immune response and not by direct oncolysis of only malignant cells, as had previously been suggested. In further support of this cell-type–nonspecific mechanism of action, T-VEC transcripts were detected in both malignant and nonmalignant cells. Taken together, these results suggest that the therapeutic action of T-VEC occurs through immunomodulation and not only via specific action on malignant cells and highlight the potential of T-VEC to treat cancers beyond melanoma, including pCBCL.

Ramelyte E, Tastanova A, Balázs Z, Ignatova D, Turko P, Menzel U, et al. Oncolytic virotherapy-mediated anti-tumor response: a single-cell perspective. Cancer Cell 2021 Mar 8 [Epub ahead of print].

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