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Paramyxoviruses for Tumor-targeted Immunomodulation: Design and Evaluation Ex Vivo
Published on: January 7, 2019
Translation of oncolytic viruses in sarcoma
Steven I Robinson1,2, Roya E Rochell2, Velia Penza2
1Division of Medical Oncology, Mayo Clinic, Rochester, MN 55902, USA.
Abstract:
Sarcomas are a rare and highly diverse group of malignancies of mesenchymal origin. While sarcomas are generally considered resistant to immunotherapy, recent studies indicate subtype-specific differences in clinical response to checkpoint inhibitors (CPIs) that are associated with distinct immune phenotypes present in sarcoma subtypes. Oncolytic viruses (OVs) are designed to selectively infect and kill tumor cells and induce intratumoral immune infiltration, enhancing immunogenicity and thereby sensitizing tumors to immunotherapy. Herein we review the accumulated clinical data evaluating OVs in sarcoma. Small numbers of patients with sarcoma were enrolled in early-stage OV trials as part of larger solid tumor cohorts demonstrating safety but providing limited insight into the biological effects due to the low patient numbers and lack of histologic grouping. Several recent studies have investigated talimogene laherparepvec (T-VEC), an approved oncolytic herpes simplex virus (HSV-1), in combination therapy regimens in sarcoma patient cohorts. These studies have shown promising responses in heavily pre-treated and immunotherapy-resistant patients associated with increased intratumoral immune infiltration. As new and more potent OVs enter the clinical arena, prospective evaluation in subtype-specific cohorts with correlative studies to define biomarkers of response will be critical to advancing this promising approach for sarcoma therapy.
Insights
Oncolytic viruses (OVs) show promise in treating rare sarcomas, even those resistant to immunotherapy. Clinical data suggest OVs enhance anti-tumor immune responses, offering a potential new therapeutic avenue for sarcoma patients.
Area of Science:
- Oncology
- Virology
- Immunotherapy
Background:
- Sarcomas are rare mesenchymal malignancies, generally resistant to immunotherapy.
- Recent research highlights subtype-specific responses to checkpoint inhibitors (CPIs) linked to immune phenotypes.
- Oncolytic viruses (OVs) selectively target tumor cells, promoting immune infiltration and enhancing immunotherapy sensitivity.
Purpose of the Study:
- To review accumulated clinical data on the efficacy of oncolytic viruses in sarcoma treatment.
- To assess the safety and biological effects of OVs in sarcoma patients.
- To explore the potential of OVs, particularly talimogene laherparepvec (T-VEC), in combination therapies for sarcoma.
Main Methods:
- Review of early-stage clinical trials involving OVs in sarcoma patients.
- Analysis of studies evaluating talimogene laherparepvec (T-VEC) in combination with other therapies for sarcoma.
- Examination of clinical data for safety, biological effects, and patient responses.
Main Results:
- Early OV trials demonstrated safety but offered limited biological insights due to small, non-specific patient numbers.
- Studies with talimogene laherparepvec (T-VEC) in sarcoma cohorts showed promising responses in pre-treated, immunotherapy-resistant patients.
- These T-VEC studies were associated with increased intratumoral immune infiltration.
Conclusions:
- Oncolytic viruses represent a promising therapeutic approach for sarcoma.
- Further prospective, subtype-specific studies with correlative biomarker analysis are crucial.
- Advancing OV therapy requires defining biomarkers to predict and enhance treatment response in diverse sarcoma subtypes.
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