Preclinical evaluation of adoptive cell therapy for patients with metastatic renal cell carcinoma.
BACKGROUND
Interleukin-2 (IL-2) shows encouraging clinical results in metastatic renal cell carcinoma (RCC) patients, but is limited by substantial toxicity. Cell-based therapy holds a promise, but past attempts in RCC were unsuccessful. Advances in tumor-infiltrating lymphocytes (TIL) generation technology and modified clinical protocols recently yielded a 50% response in refractory melanoma patients.


METHODS
RCC-derived TIL and tumor cells were processed by current protocols from tumor specimens in a clean laboratory. The expanded TIL were characterized and tested in functional assays.


RESULTS
The TIL cultures were efficiently generated and massively expanded. Virtually all the expanded cells were T-cells, but a considerable variability in the CD4/CD8 ratio and a frequent CD4-CD8-phenotype were observed. The TIL exerted cytotoxic or IFNgamma-release activities against autologous targets in major histocompatibility (MHC) class I-restricted and -independent functional patterns. The functional results were superior to former technologies.


CONCLUSIONS
Recent developments in TIL generation technology and clinical patient conditioning protocols indicate that the TIL-based approach for RCC could be revisited.
Markel
Gal
G
Ella Institute of Melanoma, Sheba Cancer Research Center, Israel.
Cohen-Sinai
Tali
T
Besser
Michal J
MJ
Oved
Kfir
K
Itzhaki
Orit
O
Seidman
Rachel
R
Fridman
Eduard
E
Treves
Avraham J
AJ
Keisari
Yona
Y
Dotan
Zohar
Z
Ramon
Jacob
J
Schachter
Jacob
J