A. Belldegrun et al., INTERFERON-ALPHA PRIMED TUMOR-INFILTRATING LYMPHOCYTES COMBINED WITH INTERLEUKIN-2 AND INTERFERON-ALPHA AS THERAPY FOR METASTATIC RENAL-CELL CARCINOMA, The Journal of urology, 150(5), 1993, pp. 1384-1390
Murine models demonstrate therapeutic synergy for the combination of i
nterleukin-2, interferon-alpha and tumor-infiltrating lymphocytes. We
treated 11 patients with metastatic renal cell carcinoma with a novel
regimen consisting of in vivo primed tumor-infiltrating lymphocytes, i
nterferon-alpha and interleukin-2. Patients received interferon-a befo
re radical nephrectomy; in vivo primed tumor-infiltrating lymphocytes
were isolated and expanded in vitro. Low dose continuous infusion inte
rleukin-2 at a dose of 2 x 10(6) units per m.2 per day was administere
d for 96 hours during each treatment week and interferon-alpha was adm
inistered as a subcutaneous injection at a dose of 6 x 10(6) units per
m.2 per day on days 1 and 4 of the interleukin-2 infusion. No therapy
was given during the last 3 days of a treatment week. One course of t
herapy consisted of 3 weeks of therapy followed by 3 weeks of rest. Pa
tients were treated until maximal response, disease progression or dos
e limiting toxicity. A maximum of 6 courses of therapy were administer
ed. Eleven patients underwent interferon-a priming and subsequent radi
cal nephrectomy. In vivo primed tumor-infiltrating lymphocytes were su
ccessfully expanded in all 11 patients with an expansion index of grea
ter than 170. In vivo primed tumor-infiltrating lymphocytes maintained
their lytic activity for greater than 5 to 8 weeks in culture as demo
nstrated in the 4-hour chromium-51 release assay. Ten patients underwe
nt multimodality biological therapy and 3 (30%, 95% confidence interva
l 6 to 65%) have achieved complete responses (2 clinical and 1 surgica
l) with durations of 24+, 23+ and 5+ months. Patients with stable dise
ase received no additional therapy. No deaths and no grade 4 toxicitie
s occurred. Immunotherapy using a combination of interferon-a primed t
umor-infiltrating lymphocytes, low dose continuous infusion interleuki
n-2 and interferon-a can induce significant and durable antitumor resp
onses in some patients with advanced renal cell carcinoma.