“NK‐like” cytotoxicity of human lymphocytes cultured in media containing fetal bovine serum

Golub, Sidney H.; Golightly, Marc G.; Zielske, John V.

doi:10.1002/ijc.2910240302

Cited by 31 publications

(11 citation statements)

References 27 publications

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“…A variety of other phenomena producing human cells lytic for tumor cells have been described, including natural killer [1,2,10,25], mixed lymphocyte-tumor reactions, some with classic CTL-type cytotoxicity [9,21,30,45,47], anomalous cytotoxicity [32], lectin incubation [23], lymphokine activation [11], activated cell killing [22], activation by BCG, tuberculin or staphylococcus filtrates [33,38], N cell activation [17], activation by xenogeneic serum [50], and activated macrophage killing [37]. The lysis demonstrated in these reports was predominantly assayed against tissue culture tumor with fresh autologous tumor target cells tested only rarely.…”

Section: Discussionmentioning

confidence: 99%

“…The demonstration of cytotoxic cells that lyse autologous tumor in humans using specific sensitization to putative tumor antigens either in vivo or in vitro has been difficult and little success has been achieved [10,21,34,45]. Recently however, Zafling et al [48] demonstrated that cells sensitized in vitro to a pool of allogeneic lymphocytes developed the ability to lyse autologous human leukemia cells.…”

Section: Introductionmentioning

confidence: 98%

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Lysis of fresh human solid tumor cells by autologous lymphocytes activated in vitro by allosensitization

Mazumder

Grimm

Rosenberg

1983

Cancer Immunol Immunother

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We have previously demonstrated that cancer patients' peripheral blood lymphocytes (PBL) allosensitized against single or pool normal donor PBL are capable of lysing fresh autologous tumor cells in a 4-h 51Cr-release assay. In this report, we present further investigations into this phenomenon. These alloactivated killer cells (A-AK cells) lysed autologous and allogeneic tumors and allogeneic but not autologous PBL. Furthermore, cold target inhibition studies demonstrated that autologous and allogeneic tumors were lysed by the same effector cells. Multiple metastases from the same patient were equivalently lysed by these A-Ak cells. The presence of adherent cells and proliferation of the precursors were necessary to generate A-AK cells, although the effector cell itself was radioresistant and nonadherent. The effects of allosensitization were enhanced by the addition of lectin-free interleukin-2 preparations to the in vitro culture by partial depletion of adherent cells prior to sensitization. The A-Ak effector cell was OKT3+, OKT8+, OKT4-, OKM1- and could be generated by just 3 days of allosensitization. The precursors for A-Ak cells could be separated from NK cells on percoll gradients and lysis could be generated from thoracic duct lymphocytes, a population devoid of NK cells. The phenotype of the majority of the precursor cells was OKT3+, OKT4-. Theses alloactivated PBL could be expanded in crude or lectin-free interleukin-2 without loss of cytotoxicity for fresh autologous tumor cells. Activated T cells represent a population of on-NK cells with broad lytic specificity for fresh tumor cells. Such cells may be of value in the adoptive immunotherapy of human solid tumors and may play a role in immune surveillance.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 98%

Lysis of fresh human solid tumor cells by autologous lymphocytes activated in vitro by allosensitization

Mazumder

Grimm

Rosenberg

1983

Cancer Immunol Immunother

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“…The LAK killing system is probably the final common pathway that explains many of the nonclassical cellular cytotoxicities reported previously, though fresh tumor cells were usually not used as target cells in such studies. These reports include activated cell ~killing (16), fetal calf serum-induced killing (19)(20)(21), and lectin-stimulated killing (18). Previous reports from our laboratory support the hypothesis that LAK may be generated from primary stimuli other than IL-2, but in which IL-2 is also generated, such as during allosensitization (23) or during lectin activation with T ceil mitogens (24), because in our reports, effectors were generated that did kill fresh autologous solid tumor cells.…”

Section: Discussionmentioning

confidence: 99%

“…Such reports include anomolous cytotoxicities, distinct from CTL during alloactivation (13)(14)(15)(16)(17), lectinactivated killing, distinct from lectin-dependent killing (18), fetal calf serum cultureinduced killers (16,(19)(20)(21), and mixed-lymphocyte tumor interaction (MLTI)-induced killers, found only when proliferation was stimulated (8)(9)(10)(11)22). Though fresh tumor targets were rarely used in those studies, our previous reports of lysis of autologous fresh solid tumor cells after allosensitization (23) or lectin activation (24), and those of others after MLTI (8)(9)(10)(11), support this hypothesis and suggest that lymphokine activated killers (LAK) represent a unique and fundamental cytotoxic effector system that may play a role in immune surveillance against NK resistant solid tumor cells, and may have a possible role in the adoptive immunotherapy of tumors.…”

mentioning

confidence: 99%

Lymphokine-activated killer cell phenomenon. Lysis of natural killer-resistant fresh solid tumor cells by interleukin 2-activated autologous human peripheral blood lymphocytes.

Grimm

Mazumder

Zhang

et al. 1982

The Journal of Experimental Medicine

2,009

629

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Activation in lectin-free interleukin 2 (IL-2) containing supernatants of peripheral blood mononuclear leukocytes (PBL) from cancer patients or normal individuals resulted in expression of cytotoxicity toward 20 of 21 natural killer (NK)-resistant fresh solid tumor cells tested. Fresh solid tumor cells were resistant to NK-mediated lysis in 10 autologous patients' PBL-tumor interactions, and from 17 normal individuals tested against 13 allogeneic fresh tumors. Culture of PBL in IL-2 for 2-3 d was required for the lymphokine activated killers (LAK) to be expressed, and lytic activity toward a variety of NK-resistant fresh and cultured tumor targets developed in parallel. Autologous IL-2 was functional in LAK activation, as well as interferon-depleted IL-2 preparations. Irradiation of responder PBL before culture in IL-2 prevented LAK development. Precursors of LAK were present in PBL depleted of adherent cells and in NK-void thoracic duct lymphocytes, suggesting that the precursor is neither a monocyte nor an NK cell. LAK effectors expressed the serologically defined T cell markers of OKT.3, Leu-1, and 4F2, but did not express the monocyte/NK marker OKM-1. Lysis of autologous fresh solid tumors by LAK from cancer patients' PBL was demonstrated in 85% of the patient-fresh tumor combinations. Our data present evidence that the LAK system is a phenomenon distinct from either NK or CTL systems that probably accounts for a large number of reported nonclassical cytotoxicities. The biological role of LAK cells is not yet known, although it is suggested that these cells may be functional in immune surveillance against human solid tumors.

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“…Biddison et al [4] and Pope et al [5] described nonspecific cytotoxic activity stimulated in vitro by tumor cells. Activated killer cells also have been generated in vitro in the presence of fetal calf scrum or other xenogenic sera [6,7], Bach et al [8] have observed this phenomenon when cytotoxic responses to a single alloantigen or to a pool of alloantigens of a species have been assessed. Also incubation of normal cells with T-cell growth factor [interleukin-2 (IL-2)] will bring about this tu mor lysis [9], Likewise, incubation of lymphocytes with concanavalin A or phytohemagglutinin will generate cells capable of tumor lysis, but incapable of lysing normal tissues [10].…”

Section: Introductionmentioning

confidence: 99%

Alloantigen-Activated Lysis of Syngenic Tumor Augmented by Allogenic Lymphocytes as Cold Targets

Sugarbaker¹,

Matthews²

1985

Oncology

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In the past, most work in tumor immunology involved attempts to demonstrate tumor-specific transplantation antigens; however, recent in vitro work has shown that it is not necessary to sensitize to a specific tumor antigen to achieve lysis of syngenic tumor cells. Responder spleen cells from B6AF₁ mice (H-2^a_’^b) were sensitized in mixed lymphocyte cultures (MLC) to alloantigens on spleen cells from B10.D2 (H-2^d) mice. In cell-mediated lympholysis (CML) assays the relevant allogenic P815 (H-2^d) tumor targets and B10.D2 lymphoblast targets were lysed. In addition, the semisyngenic tumor target EL-4 (H-2^b) was lysed but RDM-4 (H-2^k) was not. B10.BR (H-2^k), C57BL/6 (H-2^b) and B6AF₁ lymphoblasts were not lysed. If lymphocytes were added as cold targets to the CML assay, B10.D2 lymphocytes completely absorbed lytic activity when B10.D2 lymphoblasts were the target. If B10.D2 lymphocytes were added when P815 was the target, lysis was reduced but could not be abolished. When B10.D2 lymphocytes were added with EL-4 as a target, lysis doubled. These experiments show that the neoplastic determinant on tumor cells recognized by alloantigen-activated lymphocytes does not cross-react with stimulator cell alloantigen and is not an alien histocompatibility antigen. These observations should be considered when in vivo attempts are made to control tumor with in vitro activated lymphocytes; transfer of not only in vitro activated cells but also allogenic stimulator cells to the tumor site may be necessary for maximal tumor destruction.

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“NK‐like” cytotoxicity of human lymphocytes cultured in media containing fetal bovine serum

Cited by 31 publications

References 27 publications

Lysis of fresh human solid tumor cells by autologous lymphocytes activated in vitro by allosensitization

Lysis of fresh human solid tumor cells by autologous lymphocytes activated in vitro by allosensitization

Lymphokine-activated killer cell phenomenon. Lysis of natural killer-resistant fresh solid tumor cells by interleukin 2-activated autologous human peripheral blood lymphocytes.

Alloantigen-Activated Lysis of Syngenic Tumor Augmented by Allogenic Lymphocytes as Cold Targets

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