Simplified long term large scale production of highly active human lak cells for therapy

Wersäll, Peter; Masucci, Giuseppe; Pihlstedt, P; Wigzell, Hans; Mellstedt, Håkan

doi:10.1007/bf02987104

Med. Oncol. & Tumor Pharmacother.

1990

DOI: 10.1007/bf02987104

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Simplified long term large scale production of highly active human lak cells for therapy

Peter Wersäll

Giuseppe Masucci

P Pihlstedt

et al.

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1996

1997

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Cited by 2 publications

References 16 publications

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Efficient Harvest of In Vivo IL-2-Activated CD3+ Lymphocytes for Adoptive Immunotherapy by Selective Leukapheresis (Lymphocytapheresis)

Masucci¹,

Svensson²,

Hansson³

et al. 1997

Journal of Hematotherapy

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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.

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Efficient Harvest of In Vivo IL-2-Activated CD3+ Lymphocytes for Adoptive Immunotherapy by Selective Leukapheresis (Lymphocytapheresis)

Masucci¹,

Svensson²,

Hansson³

et al. 1997

Journal of Hematotherapy

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Augmentative Effects of Phytohemagglutinin‐P on Proliferation and Cytotoxicity of Interleukin‐2‐activated Canine Peripheral Blood Lymphocytes

Mizuno

Fujinaga

Kitaoka

1996

Journal of Veterinary Medicine Series A

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Canine peripheral blood lymphocytes (PBL) were stimulated with recombinant human interleukin-2 (rhIL-2) alone, or with phytohemagglutinin-P (PHA) and subsequent rhIL-2 in order to obtain large numbers of lymphokine-activated killer (LAK) cells. Incubation of PBL with rhIL-2 alone allowed proliferation of large granular lymphocyte (LGL)-like lymphocytes, and the cytotoxic activity of the lymphocytes against canine transmissible venereal sarcoma cells was detected 5-7 days after the culture onset. However, the lymphocytes died within 2 weeks of culture, resulting in limited generation of functional LAK cells. Thus, PBL pretreated with PHA were subjected to rhIL-2-dependent culture. Smallor middle-sized lymphocytes predominantly proliferated in response to rhIL-2, and proliferation of the lymphocytes was sustained for longer than 30 days by repeated stimulations with PHA and subsequent rhIL-2. Cytoroxicity reached significant levels from 2 weeks after the culture onset and thereafter remained almost constant for at least 2 weeks, leading to large-scale production of the LAK cells. Pretreatment of PBL with PHA seems to enhance the LAK cell functions through modification of the precursors of the effector LAK cells.

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Simplified long term large scale production of highly active human lak cells for therapy

Cited by 2 publications

References 16 publications

Efficient Harvest of In Vivo IL-2-Activated CD3+ Lymphocytes for Adoptive Immunotherapy by Selective Leukapheresis (Lymphocytapheresis)

Efficient Harvest of In Vivo IL-2-Activated CD3+ Lymphocytes for Adoptive Immunotherapy by Selective Leukapheresis (Lymphocytapheresis)

Augmentative Effects of Phytohemagglutinin‐P on Proliferation and Cytotoxicity of Interleukin‐2‐activated Canine Peripheral Blood Lymphocytes

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