Antitumor effects of interleukin 2 liposomes and anti-CD3-stimulated T-cells against murine MCA-38 hepatic metastasis.
The stimulation of murine splenocytes with the monoclonal antibody anti-CD3 and interleukin 2 (IL-2) results in the propagation of large numbers of cells (T-activated killer; T-AK) which demonstrate high therapeutic efficacy when infused with IL-2 into mice bearing pulmonary metastases. Interleukin 2 infusions are required to maintain the function of the adoptively transferred cells. Recent data demonstrate that the therapeutic efficacy can be enhanced by encapsulating IL-2 in liposomes. The present work tested the combination of T-AK cells with IL-2 liposomes in an immunotherapy model utilizing the MCA-38 murine colon adenocarcinoma. Expansion of murine splenocytes was achieved with anti-CD3 monoclonal antibody plus IL-2 and was consistently greater than 50-fold during a 9-day culture period. Cytolytic activity of the murine T-AK cells was mediated primarily by Lyt-2+ cells. In vivo results demonstrate synergistic therapeutic efficacy of the combination of IL-2 liposomes and T-AK cells. Evaluation of the in vivo distribution of these T-AK cells utilizing congenic mice demonstrates that Lyt-2+ cells from these in vitro cultures infiltrate hepatic metastases in vivo. The activation of lymphocytes with anti-CD3 monoclonal antibody and IL-2 appears to be a reproducible and convenient method of producing cells capable of producing antitumor effects in models of adoptive immunotherapy.
Loeffler
C M
CM
Department of Surgery, University of Minnesota, Minneapolis 55455.
Platt
J L
JL
Anderson
P M
PM
Katsanis
E
E
Ochoa
J B
JB
Urba
W J
WJ
Longo
D L
DL
Leonard
A S
AS
Ochoa
A C
AC
D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte / Q000008:administration & dosage / Q000494:pharmacology*; D017252:CD3 Complex; D003110:Colonic Neoplasms; D004337:Drug Carriers; D007376:Interleukin-2 / Q000008:administration & dosage / Q000494:pharmacology*; D008081:Liposomes; D008113:Liver Neoplasms / Q000556:secondary* / Q000628:therapy*; D016246:Lymphocytes, Tumor-Infiltrating; D051379:Mice; D008810:Mice, Inbred C57BL; D011948:Receptors, Antigen, T-Cell / Q000008:administration & dosage / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000276:immunology*
D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D004337:Drug Carriers; D007376:Interleukin-2; D008081:Liposomes; D011948:Receptors, Antigen, T-Cell