Efficient harvest of in vivo IL-2-activated CD3+ lymphocytes for adoptive immunotherapy by selective leukapheresis (lymphocytapheresis).
Autologous activated lymphocytes are an alternative to tumor-infiltrating lymphocytes for adoptive immunotherapy. We developed a method of selective lymphocytapheresis that harvests large numbers of interleukin-2 (IL-2)-activated autologous T lymphocytes. Five patients with metastatic malignant melanoma received 2.4 x 10(6) IU/m2 IL-2 sc. once a day 5 days a week for 3 weeks before lymphocytapheresis. Four patients went through lymphocytapheresis without IL-2 pretreatment. After IL-2 pretreatment, activated memory T cells increased significantly. Increasing CD3+ cells paralleled the significant enhancement of the cytotoxic activity against an HLA-A2-matched allogeneic melanoma cell line during the 3 weeks of IL-2 pretreatment. Lymphocytapheresis was performed 72 h after the last IL-2 injection to obtain the maximum recovery of activated lymphocytes at the peak of the rebound phenomenon. IL-2 pretreatment resulted in many more lymphocytes in the harvest than without pretreatment. The percentage, number, and lytic units of CD3+ cells harvested by the differential apheresis were significantly higher than were present in peripheral blood before lymphocytapheresis. These results show that pretreatment of melanoma patients with low-dose IL-2 before lymphocytapheresis allows the selective harvest of large numbers of activated T lymphocytes for adoptive immunotherapy.
Masucci
G
G
Department of Oncology, Radiumhemmet, Karolinska Hospital, Stockholm, Sweden.
Svensson
A
A
Hansson
M
M
Hansson
J
J
Nakazawa
T
T
Salazar
F
F
Petersson
M
M
Kiessling
R
R
D000328:Adult; D017252:CD3 Complex / Q000032:analysis*; D019002:CD56 Antigen / Q000032:analysis; D003601:Cytotoxicity Tests, Immunologic; D005260:Female; D006801:Humans; D016130:Immunophenotyping; D016219:Immunotherapy, Adoptive; D007376:Interleukin-2 / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use*; D007937:Leukapheresis / Q000379:methods*; D017493:Leukocyte Common Antigens / Q000032:analysis; D008213:Lymphocyte Activation; D008297:Male; D008545:Melanoma / Q000628:therapy*; D008875:Middle Aged; D010865:Pilot Projects; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology; D014407:Tumor Cells, Cultured
D017252:CD3 Complex; D019002:CD56 Antigen; D007376:Interleukin-2; D017493:Leukocyte Common Antigens