Tumor-infiltrating lymphocytes and interleukin-2: dose and schedules of administration in the treatment of metastatic cancer.
OBJECTIVE
The potential for therapeutic use of tumor-infiltrating lymphocytes (TIL), as adoptive cellular therapy has been touted for many years with some encouraging reports in patients with metastatic melanoma.


METHODS
We previously described methodologies for TIL production and phenotypic characterization of TIL generated in our laboratory between 1991 and 1995 in semipermeable bags and between 1996 and 2000 in bioreactors. Patients treated in the earlier era were to have received a hybrid bolus and a 12-hour continuous infusion of interleukin (IL)-2 (total, 48 MIU), while in the latter era 4 days of interferon- alpha preceded the TIL and IL-2; which was given by a hybrid schedule that included bolus and 72- hour continuous IL-2 (total, 96 MIU). There were 55 patients, including 23 patients with melanoma, 9 patients with renal cell carcinoma, and 8 patients with colorectal cancer. There was only 1 objective tumor response, which was noted in a patient with renal cell carcinoma. The 55 patients who received these products were grouped in cohorts by treatment era, quantity of TIL received, amount of IL-2 intended, and different combinations of TIL and IL-2.


RESULTS
There was no difference in survival by production method (treatment era), or amount of IL-2 given with TIL, but 33 patients who received an intermediate or higher dose of TIL (mean = 54.4 x 10(9)) had a median survival of 11.8 months, compared to 6.4 months for 22 patients who received 1 low-dose TIL (mean = 6.48 x 10(9)) (p = 0.059, log rank test). The objective response rate in this heterogeneous group of patients was not encouraging. The data suggest there may be a dose/benefit relationship between the total number of TIL infused and survival.
Dillman
Robert
R
Hoag Cancer Center, Newport Beach, CA 92658, USA. rdillman@hoaghospital.org
Schiltz
Patric
P
DePriest
Carol
C
Barth
Neil
N
Beutel
Linda
L
de Leon
Cristina
C
O'Connor
Audrey
A
Nayak
Shankar
S
D000293:Adolescent; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D006801:Humans; D016219:Immunotherapy, Adoptive; D007376:Interleukin-2 / Q000627:therapeutic use*; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D009362:Neoplasm Metastasis / Q000276:immunology / Q000628:therapy*; D009369:Neoplasms / Q000276:immunology / Q000628:therapy*; D015996:Survival Rate
D007376:Interleukin-2