It may alternatively be given on an inpatient basis over 1–3 days, similar to and often including the delivery of chemotherapy.Intralesional IL-2 is commonly used to treat in-transit melanoma metastases and has a high complete response rate. Local application
In preclinical and early clinical studies, local application of IL-2 in the tumor has been shown to be clinical more effective in anticancer therapy than systemic IL-2 therapy, over a broad range of doses, without serious side effects.Tumour blood vessels are more vulnerable than normal blood vessels to the actions of IL-2. When injected inside a tumor, i.e. local application, a process mechanistically similar to the vascular leakage syndrome, occurs in tumor tissue only. Disruption of the blood flow inside of the tumor effectively destroys tumor tissue.In local application, the systemic dose of IL-2 is too low to cause side effects, since the total dose is about 100 to 1000 fold lower. Clinical studies showed painful injections at the site of radiation as the most important side effect, reported by patients. In the case of irradiation of nasopharyngeal carcinoma the five-year disease-free survival increased from 8% to 63% by local IL-2 therapy

Toxicity
Systemic IL-2 has a narrow therapeutic window, and the level of dosing usually determines the severity of the side effects.
IL-2 signaling pathways and regulation
The pleiotropic effects of IL-2 are enabled due to the fact that IL-2 signal can be transduced via 3 different signaling pathways; JAK-STAT, PI3K/Akt/mTOR and MAPK/ERK pathway. After IL-2 binding to its receptor, cytoplasmatic domains of CD122 and CD132 heterodimerize. This leads to the activation of Janus kinases JAK1 and JAK3 which subsequently phosphorylate T338 on CD122. This phosphorylation recruits STAT transcription factors, predominantly STAT5, which dimerize and migrate to the cell nucleus where they bind to DNA.Gene expression regulation for IL-2 can be on multiple levels or by different ways. One of the checkpoints is signaling through TCR, antigen receptor of T-lymphocytes after recognizing MHC-peptide complex. Signaling pathway from TCR then goes through phospholipase-C (PLC) dependent pathway. PLC activates 3 major transcription factors and their pathways: NFAT, NFkB and AP-1. After costimulation from CD28 the optimal activation of expression of IL-2 and these pathways is induced. At the same time Oct-1 is expressed. It helps the activation. Oct1 is expressed in T-lymphocytes and Oct2 is induced after cell activation. NFAT has multiple family members, all of them are located in cytoplasm and signaling goes through calcineurin, NFAT is dephosphorylated and therefore translocated to the nucleus. AP-1 is a dimer and is composed of c-Jun and c-Fos proteins. It cooperates with other transcription factors including NFkB and Oct.
NFkB is translocated to the nucleus after costimulation through CD28. NFkB is a heterodimer and there are two binding sites on the IL-2 promoter.