Imaging pattern of previously in vitro sensitized and interleukin-2 expanded autologous lymphocytes in human cancer

Mukherji, Bijay; Arnbjarnarson, Oskar; Spitznagle, Larry A.; Kalish, Robert I.; Hoffman, James S.; Ergin, M. T.; Spencer, Richard P.

doi:10.1016/0883-2897(88)90012-8

“…These cells preferentially localized to the lung, liver and spleen and appeared to be promptly removed from the circulation by the reticular-endothelial system. They exhibit the same unspecific migration as heat-damaged lymphocytes (Lotze et al 1980;Mazumber et al 1984;Mukherji et al 1988), suggesting that they may have been damaged during labelling or infusion.…”

Section: Discussionmentioning

confidence: 99%

“…The distribution of peripheral blood lymphocytes sensitized against autologous tumour cells of various origins was studied by Mukherji et al (1988). He found in four of seven patients that sensitized lymphocytes showed accumulation at metastatic sites.…”

Section: Discussionmentioning

confidence: 99%

“…More recently, the ability of TILs to traffic and localise at tumour sites was demonstrated after pretreatment with cyclophosphamide and IL-2 infusion (Fisher et al 1989). Previous efforts to traffic radiolabelled LAK cells in patients with cancer of various origins failed (Lotze et al 1980;Mukherji et al 1988), or they showed poor enrichment at the tumour site in comparison with specifically tumour antigen-sensitised killer cells (Mazumber et al 1984).…”

Section: Offprint Requests To: E Sch/ifermentioning

confidence: 99%

See 1 more Smart Citation

Imaging pattern of radiolabelled lymphokine-activated killer cells in patients with metastatic malignant melanoma

Sch�fer

¹

,

Dummer

²

,

Eilles

³

et al. 1991

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Abstract. In patients with metastatic malignant melanoma the distribution patterns of radiolabelled lymphokine-activated killer (LAK) cells were investigated. Peripheral mononuclear cells (PMC) were isolated from six patients. LAK cells were generated by culturing PMC in complete medium containing 1000 U interleukin (IL)-2/ml and labelled with indium 111 before retransfer. We obtained scans at 2.5, 24, 48 or 96 h after injection with a high resolution gamma-camera. Intravenously injected LAK cells distributed to the lungs, liver, spleen and bone marrow. External tumour detection of known lymph node and bone metastases was successful in four. It failed in one patient with a solitary lung metastasis and in another patient with subcutaneous metastases. Our results suggest that LAK cells show tumour homing, providing a direct interaction between tumour and cytotoxic cells. We conclude that PMC seem to retain their ability to migrate after IL-2 stimulation and 111in_label_ ling. This technique may be helpful for kinetics studies or external detection of metastases in patients with malignant melanoma.

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“…The early distribution of activated lymphocytes pri marily to lungs, with lesser amounts to liver and spleen, does not correspond directly to the distribution of blood flow nor to the distribution of other radiolabeled leuko cytes [17], Distribution to the lungs has been noted in several studies [12][13][14][15] and cannot be accounted for by simple trapping of cells in the pulmonary capillary bed after intravenous injection as a similar distribution to lung is obtained after intra-arterial injection [18]. Spe cific interactions between lung endothelial cells and acti vated lymphocytes may be responsible for this migratory pattern [19].…”

Section: Discussionmentioning

confidence: 99%

“…Animal studies [12,13] and clinical trials [14,15] have demonstrated that activated blood and tumor-infil trating T cells distribute predominately to lung, liver and spleen. The majority of labeled cells are present in the lungs within 4 h of infusion; thereafter, radioactivity decreases in the lungs while simultaneously increasing in the liver, spleen and bone marrow.…”

Section: Discussionmentioning

confidence: 99%

Cytokine Administration Alters the Distribution of Activated Lymphocytes to the Lung

Dubinett

¹

,

Rj

²

,

Wj

³

et al. 1991

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The effects of intraperitoneal injections of recombinant interleukin-1α (IL-1; 250,000 U/day), interleukin-2 (IL-2; 50,000 units/day), interferon-γ (IFN-γ; 50,000 U/day) and tumor necrosis factor-α (TNF; 100,000 U/ day), on the biodistribution of concanavalin A (Con A)-activated, indium-Ill-labeled lympohocytes were evaluated in BALB/c mice. Syngeneic spleen cells were activated for 48 h in medium with Con A (5 µg/ml) and maintained in culture for 72 h in IL-2 (1,000 U/ml). Groups of 12 mice were treated for 4 days with either one of the cytokines or saline. On day 4, mice received 10⁷ lymphocytes (3–5 µCi) intravenously. Mice were sacrificed at 4 and 24 h following injection and the percent of administered dose per organ was determined. TNF and IL-1 produced a significant increase in lung uptake of radiolabeled lymphocytes at 4 and 24 h, whereas IL-2 and IFN-γ decreased uptake at both time points. IL-1 increased uptake by liver at 4 and 24 h while IL-2 increased uptake only at 4 h. We conclude that the distribution of activated lymphocytes following adoptive transfer is altered by cytokines. This finding may have important implications for cell delivery during adoptive immunotherapy.

show abstract

Imaging pattern of radiolabelled lymphokine-activated killer cells in patients with metastatic malignant melanoma

Schäfer

¹

,

Dummer

²

,

Eilles

³

et al. 1991

View full text Add to dashboard Cite

Abstract. In patients with metastatic malignant melanoma the distribution patterns of radiolabelled lymphokine-activated killer (LAK) cells were investigated. Peripheral mononuclear cells (PMC) were isolated from six patients. LAK cells were generated by culturing PMC in complete medium containing 1000 U interleukin (IL)-2/ml and labelled with indium 111 before retransfer. We obtained scans at 2.5, 24, 48 or 96 h after injection with a high resolution gamma-camera. Intravenously injected LAK cells distributed to the lungs, liver, spleen and bone marrow. External tumour detection of known lymph node and bone metastases was successful in four. It failed in one patient with a solitary lung metastasis and in another patient with subcutaneous metastases. Our results suggest that LAK cells show tumour homing, providing a direct interaction between tumour and cytotoxic cells. We conclude that PMC seem to retain their ability to migrate after IL-2 stimulation and 111in_label_ ling. This technique may be helpful for kinetics studies or external detection of metastases in patients with malignant melanoma.

show abstract

Imaging pattern of previously in vitro sensitized and interleukin-2 expanded autologous lymphocytes in human cancer

Cited by 13 publications

References 12 publications

Imaging pattern of radiolabelled lymphokine-activated killer cells in patients with metastatic malignant melanoma

Imaging pattern of radiolabelled lymphokine-activated killer cells in patients with metastatic malignant melanoma

Cytokine Administration Alters the Distribution of Activated Lymphocytes to the Lung

Imaging pattern of radiolabelled lymphokine-activated killer cells in patients with metastatic malignant melanoma

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