Augmentation of IL-2 activated natural killer cell adoptive immunotherapy with cyclophosphamide.
We have previously documented that adoptively transferred, IL-2 activated natural killer (A-NK) cells can accumulate within established pulmonary metastases. Since we have observed that increases in the accumulation of A-NK cells do not always lead to increases in therapeutic efficacy, we examined the ability of cyclophosphamide to enhance the therapeutic efficacy of A-NK cells. Animals with established B16 melanoma or Lewis lung carcinoma pulmonary metastases were treated with A-NK cell adoptive immunotherapy, either alone or following treatment with chemotherapeutic doses of cyclophosphamide. Adoptive immunotherapy studies with A-NK cells yielded at most a 30% reduction in the number of pulmonary metastases; however, cyclophosphamide (300 mg/kg) consistently reduced the size of metastatic colonies. In contrast, the combination therapy of A-NK cells plus cyclophosphamide was more effective than adoptive immunotherapy alone. In addition, polyethylene glycol IL-2 is superior to IL-2 in these studies.


CONCLUSIONS
Our studies suggest that chemoimmunotherapy with A-NK cells plus cyclophosphamide may be more effective than adoptive immunotherapy alone since it results in the reduction in both the size and number of pulmonary metastases.
University of Pittsburgh Cancer Institute, USA. rgoldfar@hsc.unt.edu
R H
RH
Goldfarb
M
M
Ohashi
K W
KW
Brunson
Y
Y
Kirii
Y
Y
Kotera
P H
PH
Basse
R P
RP
Kitson
D019264:Adoptive Transfer; D000818:Animals; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000627:therapeutic use*; D007376:Interleukin-2 / Q000627:therapeutic use*; D015979:Killer Cells, Lymphokine-Activated / Q000187:drug effects / Q000276:immunology*; D008175:Lung Neoplasms / Q000473:pathology / Q000556:secondary* / Q000628:therapy*; D008546:Melanoma, Experimental / Q000473:pathology / Q000556:secondary* / Q000628:therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D009362:Neoplasm Metastasis
D007376:Interleukin-2; D003520:Cyclophosphamide