Adoptive cell therapy for metastatic melanoma patients: pre-clinical development at the Sheba Medical Center.
BACKGROUND
Metastatic melanoma is an aggressive and highly malignant cancer. The 5 year survival rate of patients with metastatic disease is less than 5% with a median survival of only 6-10 months. Drugs like dacarbazin (DTIC) as a single agent or in combination with other chemotherapy agents have a response rate of 15-30%, but the duration of response is usually short with no impact on survival. Interleukin-2-based immunotherapy has shown more promising results. The National Institutes of Health recently reported that lymphodepleting chemotherapy, followed by an adoptive transfer of large numbers of anti-tumor specific tumor-infiltrating lymphocytes, resulted in an objective regression in 51% of patients.


OBJECTIVE
To introduce the TIL technology to advanced metastatic melanoma patients in Israel.


METHODS
We generated TIL cultures from tumor tissue, choosing those with specific activity against melanoma and expanding them to large numbers.


RESULTS
TIL cultures from nine patients were established and examined for their specific activity against the patients' autologous tumor cells. Twelve TIL cultures derived from 5 different patients showed the desired anti-tumor activity, making those 5 patients potential candidates for the therapy.


CONCLUSIONS
Pre-clinical studies of the TIL technology in a clinical laboratory set-up were performed successfully and this modality is ready for treating metastatic melanoma patients at the Sheba Medical Center's Ella Institute.
Besser
Michal J
MJ
Ella Institute for Treatment and Research of Melanoma, Sheba Medical Center, Tel Hashomer, Israel.
Treves
Avraham J
AJ
Itzhaki
Orit
O
Hardan
Izhar
I
Nagler
Arnon
A
Papa
Moshe Z
MZ
Catane
Raphael
R
Winkler
Eyal
E
Shalmon-Zifroni
Bruria
B
Schachter
Jacob
J
D019264:Adoptive Transfer / Q000379:methods*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D066298:In Vitro Techniques; D016131:Lymphocyte Subsets / Q000637:transplantation; D016246:Lymphocytes, Tumor-Infiltrating / Q000637:transplantation; D008297:Male; D008545:Melanoma / Q000556:secondary* / Q000628:therapy*; D016896:Treatment Outcome; D014407:Tumor Cells, Cultured