L-24: A novel gene therapy candidate for immune system upregulation in Hodgkin's lymphoma

Hodgkin’s Lymphoma (HL) as a prevalent hematolymphoid malignancy begins in cells of immune system and is characterized by the specific histologic, clinical properties. Abnormality in apoptosis has been recognized as a crucial pathway in its progression. Nowadays, 35–40% of patients in stages III and IV show disease relapse or symptoms of refractory to first-line chemotherapy; therefore, novel treatment strategies are required. As apoptosis inducing is an important mechanism in cancer treatments, novel anticancer molecules to induce programmed cell death are required. The authors present a novel therapeutic approach for HL, with regard to anti-tumoral and immunomodulatory effects of the mda-7/IL-24. This gene, located in human chromosome 1q32-33, has shown tumor suppressor activity in various human malignant cells in, in vitro, in vivo, and even in clinical trial studies. Our hypothesis was designed to evaluate anti- tumoral effects of mda-7/IL-24 in SCID mice model using the adenovirus-based vector. mda-7/IL-24 interestingly has antiangiogenic, immunomodulatory, and bystander antitumoral activities. mda-7/IL-24 can suppress anti-apoptotic Bcl-2 family proteins, and induces GADD family, Bak, Bax, and other pro-apoptosis proteins. This hypothesis suggests that adenovirus vectors expressing mda-7/IL-24 may help for effective immunotherapies of HL.