Adoptive transfer of human natural killer cells in mice with severe combined immunodeficiency inhibits growth of Hsp70-expressing tumors

In vitro, tumor-selective Hsp70 plasma membrane localization correlates wit h increased sensitivity to lysis mediated by a subpopulation of human natur al killer (NK) cells that adhere to plastic following cytokine stimulation. In the present study, we analyzed the capacity of adoptively transferred h uman NK cells in SCID/beige mice for local tumor control and prevention of metastatic dissemination of Hsp70-expressing CX+ and non-expressing CX- tum ors following orthotopic (o.t.) injection. Both tumor sublines were derived by cell sorting of the original cell line, CX2, and thus exhibit an identi cal MHC and adhesion molecule expression pattern but differ with respect to Hsp70 plasma membrane expression. Viability of adherent, human NK cells in SCID/beige mice up to 18 days and the capacity to migrate have been demons trated. Growth of Hsp70-expressing and non-expressing CX+ and CX- tumor cel ls was completely suppressed when 10 x 10(6) NK cells were injected into th e i.p. cavity on day 4 after inoculation of 2.5 x 10(6) tumor cells, Althou gh a single injection of 5 or 2.5 x 10(6) NK cells was not sufficient to su ppress tumor growth completely in all mice, the reduction in size of CX+ tu mors was significantly greater than that of CX- tumors. To mimic the clinic al situation, ex vivo stimulated NK cells were injected i.v. on day 4 after o.t. injection of tumor cells. Under these conditions, growth of Hsp70-exp ressing primary tumors and metastases was suppressed. If CX tumor cells wer e injected, 3 of 9 mice developed Hsp70-negative primary tumors. However, n one of these mice developed distant metastases, In summary, our data indica te that Hsp70 acts as a recognition structure for adherent NK cells in a SC ID/beige mouse model. (C) 2000 Wiley-Liss, Inc.