Radiotherapy in Combination With Cytokine Treatment

Abstract

Radiotherapy (RT) plays an important role in the management of cancer patients. RT is used in more than 50% of patients during the course of their disease in a curative or palliative setting. In the past decades it became apparent that the abscopal effect induced by RT might be dependent on the activation of immune system, and that the induction of immunogenic cancer cell death and production of danger-associated molecular patterns from dying cells play a major role in the radiotherapy-mediated anti-tumor efficacy. Therefore, the combination of RT and immunotherapy is of a particular interest that is reflected in designing clinical trials to treat patients with various malignancies. The use of cytokines as immunoadjuvants in combination with RT has been explored over the last decades as one of the immunotherapeutic combinations to enhance the clinical response to anti-cancer treatment. Here we review mainly the data on the efficacy of IFN-α, IL-2, IL-2-based immunocytokines, GM-CSF, and TNF-α used in combinations with various radiotherapeutic techniques in clinical trials. Moreover, we discuss the potential of IL-15 and its analogs and IL-12 cytokines in combination with RT based on the efficacy in preclinical mouse tumor models.

Development of hematopoietic syndrome mice model for localized radiation exposure

“…The whole body H-ARS models have been used to study the survival efficacy of potential radioprotectors and mitigators candidates, for dose optimization of candidate MCMs, polypharmacy of MCMs, and in pharmacokinetic/ pharmacodynamic studies [19][20][21][22][23] . Recently, animal models are studied for H-ARS treatment by the administration of cytokines and/ or stem cells [24][25][26] . These models may not be sufficient to precisely simulate the risk of irradiation in scenarios involving facility accidents, dirty bomb explosion and radioisotope handling contamination accidents where exposures are mainly non-uniform or heterogeneous 7,[27][28][29][30][31] .…”

Radiation Therapy as a Modality to Create Abscopal Effects: Current and Future Practices

“…Observations show that AbEs traverse into the blood-brain, hence becoming a barrier [11]. This case demonstrates the role of radiations in ensuring the release of disruptions to the blood-brain barrier and tumorassociated antigens [12]. AbEs are mainly sporadic events of tumors that begin to grow following RT treatments as observed through irradiated sites from a distance [13].…”

Charged Particle and Conventional Radiotherapy: Current Implications as Partner for Immunotherapy

“…However, even if immune cells are actively attracted to the tumor site, stimuli are still needed to target tumor cells. The combination with RT can provide this stimuli effectively [ 144 ]. The IL2-NHS immunocytokine consisting of a human NHS76 (antibody specific for necrotic DNA) fused to genetically modified human IL2, administered three days after the end of fRT (5 × 3.6 Gy), resulted in greater growth inhibition than either therapy alone in the mouse lung tumor model LLC [ 145 ], supporting the use in lung cancer patients.…”