Trial Watch—Immunostimulation with cytokines in cancer therapy

Abstract

During the past decade, great efforts have been dedicated to the development of clinically relevant interventions that would trigger potent (and hence potentially curative) anticancer immune responses. Indeed, developing neoplasms normally establish local and systemic immunosuppressive networks that inhibit tumor-targeting immune effector cells, be them natural or elicited by (immuno)therapy. One possible approach to boost anticancer immunity consists in the (generally systemic) administration of recombinant immunostimulatory cytokines. In a limited number of oncological indications, immunostimulatory cytokines mediate clinical activity as standalone immunotherapeutic interventions. Most often, however, immunostimulatory cytokines are employed as immunological adjuvants, i.e., to unleash the immunogenic potential of other immunotherapeutic agents, like tumor-targeting vaccines and checkpoint blockers. Here, we discuss recent preclinical and clinical advances in the use of some cytokines as immunostimulatory agents in oncological indications.

Preclinical evaluation of a MAGE-A3 vaccination utilizing the oncolytic Maraba virus currently in first-in-human trials

“…1,2 Since then, checkpoint inhibitors have supplanted dacarbazine and quadrupled long-term survival. 3–6 Although checkpoint inhibitors have garnered much attention, 1,2,7 other biotherapetics have been approved including immunostimulatory cytokines, 8 monoclonal antibodies, 9 cancer vaccines, 10 oncolytic virotherapy 11,12 and chimeric antigen receptor (CAR) T-cell therapy. 13 All these approaches invoke immunity through non-redundant mechanisms of action.…”

NK-Cell Recruitment Is Necessary for Eradication of Peritoneal Carcinomatosis with an IL12-Expressing Maraba Virus Cellular Vaccine

“…The therapeutic benefit achieved with boosting NK-cell activation and cytolytic activity through cytokine therapy has previously been reported for a number of cancers (9). IL12, arguably one of the best characterized proinflammatory cytokines, is a potent stimulator of NK cell-mediated tumor cell killing (10)(11)(12).…”

Official Medications for Anti-Tumor Gene Therapy

“…На место каждого нефункционирующего гена RL1 была по-мещена кассета, кодирующая ген гранулоцитарно-макро-фагального колониестимулирующего фактора (GM-CSF) под цитомегаловирусным (CMV) промотором. Экспрессия GM-CSF в условиях вирусного лизиса опухолевых клеток способствует рекрутингу и активации антигенпрезенти-рующих клеток, таким образом усиливая противоопухоле-вый иммунный ответ организма [60,61]. Важно отметить, что T-VEC сохраняет чувствительность к противовирусным препаратам, например, к ацикловиру.…”