Oncolytic Virotherapy and Microenvironment in Multiple Myeloma

Multiple myeloma (MM) is a hematologic malignancy characterized by the accumulation of bone marrow (BM) clonal plasma cells, which are strictly dependent on the microenvironment. Despite the improvement of MM survival with the use of new drugs, MM patients still relapse and become always refractory to the treatment. The development of new therapeutic strategies targeting both tumor and microenvironment cells are necessary. Oncolytic virotherapy represent a promising approach in cancer treatment due to tumor-specific oncolysis and activation of the immune system. Different types of human viruses were checked in preclinical MM models, and the use of several viruses are currently investigated in clinical trials in MM patients. More recently, the use of alternative non-human viruses has been also highlighted in preclinical studies. This strategy could avoid the antiviral immune response of the patients against human viruses due to vaccination or natural infections, which could invalid the efficiency of virotherapy approach. In this review, we explored the effects of the main oncolytic viruses, which act through both direct and indirect mechanisms targeting myeloma and microenvironment cells inducing an anti-MM response. The efficacy of the oncolytic virus-therapy in combination with other anti-MM drugs targeting the microenvironment has been also discussed.

Automated summary

Multiple myeloma is a hematologic malignancy that depends on the microenvironment, and despite improvements in survival with new drugs, drug resistance and relapse remain issues, necessitating the development of new treatment strategies. Oncolytic virotherapy shows promise in cancer treatment, with various human viruses being studied in preclinical models and in clinical trials for MM patients, while the use of non-human viruses is also being explored to potentially avoid immune responses that could reduce efficacy.