Oncolytic virotherapy for treatment of breast cancer, including triple-negative breast cancer.

Breast cancer is a heterogeneous disease, characterized by several distinct biological subtypes, among which triple-negative breast cancer (TNBC) is one associated with a poor prognosis. Oncolytic virus replication is an immunogenic phenomenon, and viruses can be armed with immunostimulatory molecules to boost virus triggered antitumoral immune responses. Cyclophosphamide (CP) is a chemotherapy drug that is associated with cytotoxicity and immunosuppression at higher doses, whereas immunostimulatory and anti-angiogenic properties are observed at low continuous dosage.

Predictive and Prognostic Clinical Variables in Cancer Patients Treated With Adenoviral Oncolytic Immunotherapy.

The development of oncolytic viruses has recently made great progress towards being available to cancer patients. With the breakthrough into clinics, it is crucial to analyze the existing clinical experience and use it as a basis for treatment improvements. Here, we report clinical data from 290 patients treated with oncolytic adenovirus.

Phase I study with ONCOS-102 for the treatment of solid tumors - an evaluation of clinical response and exploratory analyses of immune markers.

Background: We conducted a phase I study with a granulocyte macrophage colony stimulating factor (GMCSF)-expressing oncolytic adenovirus, ONCOS-102, in patients with solid tumors refractory to available treatments. The objectives of the study were to determine the optimal dose for further use and to assess the safety, tolerability and adverse event (AE) profile of ONCOS-102. Further, the response rate and overall survival were evaluated as well as preliminary evidence of disease control.

Treatment of melanoma with a serotype 5/3 chimeric oncolytic adenovirus coding for GM-CSF: Results in vitro, in rodents and in humans.

Metastatic melanoma is refractory to irradiation and chemotherapy, but amenable to immunological approaches such as immune-checkpoint-inhibiting antibodies or adoptive cell therapies. Oncolytic virus replication is an immunogenic phenomenon, and viruses can be armed with immunostimulatory molecules. Therefore, oncolytic immuno-virotherapy of malignant melanoma is an appealing approach, which was recently validated by a positive phase 3 trial.

Serotype chimeric oncolytic adenovirus coding for GM-CSF for treatment of sarcoma in rodents and humans.

Sarcomas are a relatively rare cancer, but often incurable at the late metastatic stage. Oncolytic immunotherapy has gained attention over the past years, and a wide range of oncolytic viruses have been delivered via intratumoral injection with positive safety and promising efficacy data. Here, we report preclinical and clinical results from treatment of sarcoma with oncolytic adenovirus Ad5/3-D24-GMCSF (CGTG-102).

Fc-gamma receptor polymorphisms as predictive and prognostic factors in patients receiving oncolytic adenovirus treatment.

Background: Oncolytic viruses have shown potential as cancer therapeutics, but not all patients seem to benefit from therapy. Polymorphisms in Fc gamma receptors (FcgRs) lead to altered binding affinity of IgG between the receptor allotypes and therefore contribute to differences in immune defense mechanisms. Associations have been identified between FcgR polymorphisms and responsiveness to different immunotherapies.

Antiviral and antitumor T-cell immunity in patients treated with GM-CSF-coding oncolytic adenovirus.

Purpose: Multiple injections of oncolytic adenovirus could enhance immunologic response. In the first part of this article, the focus was on immunologic aspects. Sixty patients previously naïve to oncolytic virus and who had white blood cells available were treated.