Oncolytic Virotherapy Development for Hematologic Malignancies
Hematological malignancies usually affect individuals older than 60 years of age, including lymphomas, leukemias, multiple myeloma (MM), and the myelodysplastic syndromes (MDSs). As a high-risk disease, hematopoietic stem cell transplant (HCT) can be used for the treatment. Nevertheless, in the setting of autologous HCT, relapse on account of contamination of the autograft with cancer cells remains a big challenge. Besides, ex vivo manipulations of the autograft to purge cancer cells via chemotherapies and toxins have been explored. To date, the ideal ex vivo purging agent should contain several features, such as selectively targeting the contaminating cancer cells while sparing normal stem and progenitor cells, as well as used quickly without toxicities to the recipient. Oncolytic Virus (OV) is a suitable agent meeting these criteria. With excellent specialists and ample experience in immunotherapy, Creative Biolabs has established an advanced OncoVirapy™ platform. With our full-scale OVs platform, our scientists are capable of developing specific oncolytic virotherapy strategy for hematologic malignancies, as well as providing OVs construction and validation services to customers all over the world.
Fig 1. Schema of oncolytic virotherapy treatment for patients with hematological malignancies undergoing high-dose chemotherapy and autologous HCT. (Bais, S., 2012)
Purging Strategies for Hematologic Malignancies
Because of the high rates of refractory and relapsed in patients with hematological malignancies, as well as the proof of contaminating cancer cells in autologous HCT grafts, graft purging of contaminating cells seems to be a possible approach to increase posttransplant disease-free and overall survival. Typically, a safe and effective purging scheme should specifically target the contaminating malignant clone, meanwhile, spare common HSPC required for reconstitution of immunity, erythropoieis, and platelets. Until now, a variety of purging strategies have been explored to selectively target malignant cells from autologous HCT grafts. One common strategy is to treat the autologous graft after collection but prior to transplant back into the patient. Several these ex vivo purging strategies have been studied, for example, chemotherapy with antiproliferative drugs, CD34+ stem/progenitor cell enrichment using immunomagnetic selection, immunotoxins or hybrid cytotoxic proteins designed to selectively kill cancer cells, as well as monoclonal antibodies.
Oncolytic Virotherapy for Hematological Malignancies
Due to the special characteristics of OVs, they are considered as ideal purging agents for hematological malignancies. Specifically, certain OVs selectively target malignant hematopoietic cells, for example, multiple myeloma and leukemia cells while sparing normal HSPCs. This ability to purge autologous HCT grafts allows OVs highly attractive for potential use in the clinical transplant setting. At present, several OVs have already been translated into the clinic. For instance, coxsackievirus A21 (CVA21), a common enterovirus, displayed a powerful cytostatic and cytocidal effect against three MM cell lines with decreased cytotoxicity against normal human peripheral blood mononuclear cells (PBMCs). There are also several other OVs attempted for hematological malignancies purging, including Reovirus, Vesicular stomatitis virus (VSV), Live attenuated measles virus (MV), Oncolytic rat parvovirus, myxoma virus (MYXV), and Tumor-specific double-deleted Vaccinia virus.
With the rapid progress of novel therapeutic strategies in hematological malignancies, OVs continue to hold promising as an effective treatment. Based on our advanced OncoVirapy™ platform, Creative Biolabs is confident in providing novel OVs and developing more efficient oncolytic virotherapy strategies for our customers.
Reference:
- Bais, S., (2012). "Oncolytic virotherapy for hematological malignancies." Advances in virology, 2012.
- Domingo-Musibay, E., (2016). "Gene and virotherapy for hematological malignancies." International journal of hematology, 104(1), 29-41.