Glioblastoma is one of the most difficult tumor types to treat with conventional therapy options like tumor debulking and chemo- and radiotherapy. Immunotherapeutic agents like oncolytic viruses, immune checkpoint inhibitors, and chimeric antigen receptor T cells have revolutionized cancer therapy, but their success in glioblastoma remains limited and further optimization of immunotherapies is needed. Several oncolytic viruses have demonstrated the ability to infect tumors and trigger anti-tumor immune responses in malignant glioma patients. Leading the pack, oncolytic herpesvirus, first in its class, awaits an approval for treating malignant glioma from MHLW, the federal authority of Japan. Nevertheless, some major hurdles like the blood–brain barrier, the immunosuppressive tumor microenvironment, and tumor heterogeneity can engender suboptimal efficacy in malignant glioma. In this review, we discuss the current status of malignant glioma therapies with a focus on oncolytic viruses in clinical trials. Furthermore, we discuss the obstacles faced by oncolytic viruses in malignant glioma patients and strategies that are being used to overcome these limitations to (1) optimize delivery of oncolytic viruses beyond the blood–brain barrier; (2) trigger inflammatory immune responses in and around tumors; and (3) use multimodal therapies in combination to tackle tumor heterogeneity, with an end goal of optimizing the therapeutic outcome of oncolytic virotherapy.

We conclude that TANVΔ66R/mIL-2 is potentially therapeutic for human melanomas in the absence of T cells, and IL-2 expression resulted in an overall increase of therapeutic efficacy.

Breast cancer (BC) is the most common type of cancer among women and is the second most common cause of cancer-related deaths, following lung cancer. Severe toxicity associated with a long-term use of BC chemo- and radiotherapy makes it essential to look for newer therapeutics. Additionally, molecular heterogeneity at both intratumoral and intertumoral levels among BC subtypes is known to result in a differential response to standard therapeutics. Oncolytic viruses (OVs) have emerged as one of the most promising treatment options for BC. Many preclinical and clinical studies have shown that OVs are effective in treating BC, both as a single therapeutic agent and as a part of combination therapies. Combination therapies involving multimodal therapeutics including OVs are becoming popular as they allow to achieve the synergistic therapeutic effects, while minimizing the associated toxicities. Here, we review the OVs for BC therapy in preclinical studies and in clinical trials, both as a monotherapy and as part of a combination therapy. We also briefly discuss the potential therapeutic targets for BC, as these are likely to be critical for the development of new OVs.

Glutamic acid and alanine make up more than 60 per cent of the total amino acids in the human body. Glutamine is a significant source of energy for cells and also a prime donor of nitrogen in the biosynthesis of many amino acids. Several studies have advocated the role of glutamic acid in cancer therapy. Identification of metabolic signatures in cancer cells will be crucial for advancement of cancer therapies based on the cell’s metabolic state. Stable nitrogen isotope ratios (15N/14N, δ15N) are of particular advantage to understand the metabolic state of cancer cells, since most biochemical reactions involve transfer of nitrogen. In our study, we used the natural abundances of nitrogen isotopes (δ15N values) of individual amino acids from human colorectal cancer cell lines to investigate isotope discrimination among amino acids. Significant effects were noticed in the case of glutamic acid, alanine, aspartic acid and proline between cancer and healthy cells. The data suggest that glutamic acid is a nitrogen acceptor while alanine, aspartic acid and proline are nitrogen donors in cancerous cells. One plausible explanation is the transamination of the three acids to produce glutamic acid in cancerous cells.

Neuregulin (NRG), an epidermal growth factor is known to promote the growth of various cell types, including human melanoma cells through ErbB family of tyrosine kinases receptors. Tanapoxvirus (TPV) encoded protein TPV-15L, a functional mimic of NRG, also acts through ErbB receptors. Here, we show that the TPV-15L protein promotes melanoma proliferation. TPV recombinant generated by deleting the 15L gene (TPVΔ15L) showed replication ability similar to that of wild type TPV (wtTPV) in owl monkey kidney (OMK) cells, human lung fibroblast (WI-38) cells and human melanoma (SK-MEL-3) cells. Whereas, a TPV recombinant with both 15L and the thymidine kinase (TK) gene (66R) ablated (TPVΔ15LΔ66R) replicated less efficiently than TPVΔ15L and the parental virus. TPVΔ15L exhibited more robust tumor-regression in the melanoma-bearing nude mice than other TPV recombinants. Our results indicate that deletion of TPV-15L gene product which facilitates the growth of human melanoma cells can be an effective strategy to enhance the oncolytic potential of TPV for the treatment of melanoma.