Effect of CD3 antibodies on cytotoxicity against leukemic cells resistant to activated killer cells

Reizenstein, Peter; Vasilopoulos, George

doi:10.1016/0145-2126(89)90172-0

Cited by 3 publications

(2 citation statements)

References 6 publications

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“…We have observed that at least for LAK effectors, it is often the case that fresh CML cells are resistant to lysis [24]. This relative resistance to lysis is a phenomenon previously noted for certain other types of leukaemia and lymphoma cells as well [8,9,16,20,21,26].…”

Section: Discussionmentioning

confidence: 93%

“…Major-histocompatibility-complex(MHC)-unrestricted cytotoxicity with some tumour selectivity induced by this procedure is thought likely to contribute to the success of such immunotherapy, although several preclinical studies have suggested that fresh leukaemia cells may be relatively resistant to LAK and activated natural killer (NK) cell lysis [1,8,9,16,20,26], with the possibility that myeloid cells are eren less sensitive than lymphoid cells [21]. In the case of CML, we documented a defect in LAK cell induction in chronic-phase patients' peripheral blood, which was at least partially corrected after therapy with IFNo~ [25].…”

Section: Introductionmentioning

confidence: 99%

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Susceptibility of autologous target cells to lysis by lymphokine-activated effectors from interferon-α-treated chronic myelogenous leukaemia patients

Pawelec

Ehninger

Schmidt

et al. 1990

Cancer Immunol Immunother

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Chronic myelogenous leukemia (CML) patients in chronic phase display compromised lymphokine-activated killer (LAK) cell induction, which is partly restored after therapy with interferon alpha. However, the relative resistance of the leukemic cells from these patients to autologous or allogeneic LAK lysis is not affected by this treatment. In an attempt to render CML cells more susceptible to lysis or cytostasis, they were precultured in serum-free medium with or without recombinant growth factors. In eight patients studied, interleukin-3 (IL-3) significantly enhanced the spontaneous short-term (6-day) proliferation of CML cells, with retention of ability to form colonies in methylcellulose. Culture in either medium alone or IL-3 led to a significant enrichment of CD14+ and CD33+ cells but to a reduction in CD34+ cells. In contrast, culture of the same cells in IL-2 (to generate autologous LAK activity) resulted in a loss of CD14+ and CD33+ as well as CD34+ cells but in a significant increase in CD3+ and CD56+ cells. Despite similarities in their phenotypes, IL-3 cultured cells but not those cultured in medium alone acquired susceptibility to lysis by the IL-2-cultured autologous LAK cells. These results may have significance for the design of novel combination immunotherapy in CML.

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