TY - JOUR
T1 - Selection of Gene-Marked Tumor Infiltrating Lymphocytes from Post-Treatment Biopsies
T2 - A Case Study
AU - Aebersold, Paul
AU - Kasid, Attan
AU - Rosenberg, Steven A.
PY - 1990/12/1
Y1 - 1990/12/1
N2 - Patients with malignant melanoma have been treated with interleukin-2 (IL-2) and tumor-infiltrating lymphocytes (TIL) marked by retroviral gene transduction. The retroviral vector contained a gene coding for the bacterial enzyme neomycin phosphotransferase, such that transduced TIL expressing the enzyme could survive otherwise toxic concentrations of the neomycin analogue G418. For 1 patient, who exhibited a complete regression of cancer after treatment with TIL, lymphocytes from post-treatment blood and tumor biopsies were cultured in IL-2, and transduced TIL were recovered by G418 selection. Analysis of T-cell receptor heterogeneity indicated that the transduced TIL recovered from the tumor biopsy were different from TIL that were kept strictly in vitro and selected in G418. The selection process required weeks in culture, during which time control cultures changed radically in subset composition, so there was also a simultaneous selection for long-term in vitro growth advantage. It cannot be certain that the TIL subsets preferentially recovered from the tumor biopsy corresponded to those that mediated complete elimination of tumor in this patient.
AB - Patients with malignant melanoma have been treated with interleukin-2 (IL-2) and tumor-infiltrating lymphocytes (TIL) marked by retroviral gene transduction. The retroviral vector contained a gene coding for the bacterial enzyme neomycin phosphotransferase, such that transduced TIL expressing the enzyme could survive otherwise toxic concentrations of the neomycin analogue G418. For 1 patient, who exhibited a complete regression of cancer after treatment with TIL, lymphocytes from post-treatment blood and tumor biopsies were cultured in IL-2, and transduced TIL were recovered by G418 selection. Analysis of T-cell receptor heterogeneity indicated that the transduced TIL recovered from the tumor biopsy were different from TIL that were kept strictly in vitro and selected in G418. The selection process required weeks in culture, during which time control cultures changed radically in subset composition, so there was also a simultaneous selection for long-term in vitro growth advantage. It cannot be certain that the TIL subsets preferentially recovered from the tumor biopsy corresponded to those that mediated complete elimination of tumor in this patient.
UR - http://www.scopus.com/inward/record.url?scp=0025619343&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0025619343&partnerID=8YFLogxK
U2 - 10.1089/hum.1990.1.4-373
DO - 10.1089/hum.1990.1.4-373
M3 - Article
C2 - 1964094
AN - SCOPUS:0025619343
SN - 1043-0342
VL - 1
SP - 373
EP - 384
JO - Human gene therapy
JF - Human gene therapy
IS - 4
ER -