Research ArticleTumor Radiotherapy

Phase 1 Study of Stereotactic Body Radiotherapy and Interleukin-2—Tumor and Immunological Responses

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Science Translational Medicine  06 Jun 2012:
Vol. 4, Issue 137, pp. 137ra74
DOI: 10.1126/scitranslmed.3003649

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Despite decades of research into causes and potential therapies for cancer, cancers still account for almost 13% of all deaths every year. It is becoming increasingly clear that monotherapies are not the answer, and combining drugs to improve efficacy and prevent resistance is becoming the norm. However, care must be taken when combining even drugs already in the clinic—two treatments may not necessarily be better than one and may even cause harm. Thus, there is a need for rationally designed combination therapy. Here, Seung et al. conduct a phase 1 trial on one such rationally combined therapy—interleukin-2 (IL-2) and stereotactic body radiation therapy (SBRT).

IL-2, an immune activator, has been long used in the clinic either as a single-agent immunotherapy or in combination with various drugs for melanoma and renal cell carcinoma, with limited success. Here, the authors combine high-dose IL-2 with targeted radiation therapy based on clinical observation of enhanced efficacy in patients as well as the still to be proven hypothesis that radiation damage induces tumor antigen release and microenvironment changes that should enhance the immune-activating effects of IL-2. They found that the combination therapy was safe, and, albeit in a small number of patients, appeared to have improved efficacy over IL-2 alone. Intriguingly, they found a greater frequency of proliferating early effector memory T cells in the peripheral blood of these patients. Although studies with more patients and more detailed mechanistic follow-up must be performed, this study suggests that the rational combination of SBRT and IL-2 may improve upon current therapies for metastatic melanoma and renal cell carcinoma.