In this i-SABR (immunotherapy + Stereotactic Ablative Body Radiation) trial, the stereotactic radiation to multiple metastatic sites is delivered not only to eradicate sites of bulky progressive disease, but also to provide antigen presentation and immune stimulation which is expected to act synergistically when immediately followed by the non-specific immune stimulation provided by treatment with HD IL-2 and thereby increase the response rate and complete response for metastatic clear cell renal cell cancer patients. Both HD IL-2 and SABR are FDA approved therapeutic cancer treatment

Inclusion Criteria:

1. Biopsy-proven metastatic clear cell RCC.

2. Radiographic evidence of metastatic disease. 2.1 Patients with any number of metastatic site are allowed to enroll. However, only up to six sites will be selected for SBRT treatment, at the discretion of the treating radiation oncologist.

3. Patient must have ≥1 lesion of size >1.5cm.

4. Previous treatment with surgery, radiation, chemotherapy, immunotherapy or any targeted agents are allowed 28 days before the start of HD IL-2

5. Age ≥ 18 years.

6. Performance status ECOG 0, 1.

7. Patient must be eligible for HD IL-2 treatment

8. Patient must be eligible for SABR to one or more extra cranial sites.

9. Adequate organ and marrow function as defined below:

   • leukocytes ≥ 3,000/mcL
   • absolute neutrophil count ≥ 1,500/mcL
   • platelets ≥ 50,000/mcl
   • total bilirubin ≤ 2mg/dL
   • AST(SGOT)/ALT(SPGT) ≤ 2.5 X institutional upper limit of normal

10. Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.

    10.1 A female of child-bearing potential is any woman (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria:

    • Has not undergone a hysterectomy or bilateral oophorectomy; or
    • Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months).

11. Ability to understand and the willingness to sign a written informed consent

12. Adequate Renal function with Cr ≤ 1.6 mg/dL.

13. Adequate cardiac function (adequate perfusion; no ischemia) on thallium (or Tc) stress test

14. Adequate pulmonary function on PFT (FEV1 >65%; DLCO>60%).

Exclusion Criteria:

1. Subjects who have had chemotherapy or radiotherapy within 4 weeks prior to entering the study
2. History of HIV, Hepatitis B, Hepatitis C and HTLV serology
3. Subjects may not be receiving any other investigational or standard antineoplastic agents.
4. Subjects with known brain metastases should be excluded from this clinical trial because of their poor prognosis
5. Subjects with life expectancy < 6 months.
6. History of allergic reactions to recombinant IL-2
7. Uncontrolled recurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia,.
8. Psychiatric illness/social situations that would limit compliance with study requirements.
9. Subjects must not be pregnant or nursing due to the potential for congenital abnormalities and the potential of this regimen to harm nursing infants.
10. Systemic or topical steroid use or other immunosuppressive therapy within the past 28 days
11. Subjects required to take corticosteroids or other immunosuppressive therapy such as those with organ allograft

4 years