Generation and partial characterization of melanoma sublines resistant to lymphokine activated killer (LAK) cells. Relevance to doxorubicin resistance.

To see whether a tumor cell population may contain cells resistant to lymphokine-activated killer (LAK) lymphocytes, cells from a LAK-sensitive melanoma line (Me 665/2) were co-cultured with LAKs. Three sublines were obtained after 1, 2 or 3 immunoselection cycles. Immunoselected (IS) sublines show reduced proliferation, decreased reactivity to the monoclonal antibody (MAb) R24 and appeared morphologically more differentiated in comparison with the parental Me 665/2 line.

In vitro lymphocyte response to autologous melanoma: clues in designing new adoptive immunotherapy protocols.

Recent studies indicate that different types of antitumour lymphocytes (T and non-T) can be generated in vitro and in vivo after exposure to recombinant interleukin-2 (rIL-2). In vitro it is possible to selectively expand the CD3 cells by using anti-CD3 monoclonal antibody and rIL-2. Adherence can select a minor subpopulation of lymphokine-activated killer (LAK) cells (A-LAK) endowed with a higher lytic activity.

Susceptibility of human and murine drug-resistant tumor cells to the lytic activity of rIL2-activated lymphocytes (LAK).

This article surveys the available data on the sensitivity of drug-resistant tumor cells to recombinant interleukin 2 (rIL2)-activated lymphocytes (LAK). In our own study, three different experimental systems were used: 1. in vitro treatment of tumor cells with an anticancer drug followed by the use of surviving cells as targets of LAK; 2.

A new procedure for large scale production and freezing of lymphokine activated killer (LAK) cells to be used in adoptive immunotherapy of cancer.

A new procedure for activation of peripheral blood lymphocytes (PBL) with recombinant interleukin 2 (rIL2) is described. PBL obtained by leukapheresis were subjected to NH4Cl (ACK) treatment to clear erythrocyte contamination; Ficoll separation was not performed. PBL were subsequently seeded in 10-floor multitrays (Cell FactoryTM, CF), gasified and incubated at 37 degrees C for 3-4 days in a humidified 5% CO2 atmosphere.

Differential lysis of melanoma clones by autologous recombinant interleukin 2-activated lymphocytes. Relationship with spontaneous resistance to doxorubicin (Dx).

To investigate whether human melanoma cells intrinsically resistant to autologous LAKs do exist, and whether a relationship between the level of lysis of LAKs and spontaneous drug resistance can be identified at the clonal level, we studied 44 clones obtained from a metastatic melanoma lesion. The antigenic phenotype of clones revealed a marked heterogeneity in the expression of HLA antigens of classes I and II. The clones were subsequently tested for sensitivity to autologous LAK and for spontaneous resistance to Dx.

Susceptibility of chemoresistant murine and human tumor cells to lysis by interleukin 2-activated lymphocytes.

The sensitivity of three different human and murine doxorubicin (Dx)-sensitive or -resistant pairs of tumor cells to recombinant interleukin 2 (rIL2)-activated lymphocytes was studied. In two pairs of these sublines (LoVo human colon carcinoma and B16 mouse melanoma sublines), resistance to Dx was induced in vitro, while in the third pair (9229 human metastatic melanoma clones), Dx resistance was spontaneously present in clone 9229.24.