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.
Goldfarb
R H
RH
University of Pittsburgh Cancer Institute, USA. rgoldfar@hsc.unt.edu
Ohashi
M
M
Brunson
K W
KW
Kirii
Y
Y
Kotera
Y
Y
Basse
P H
PH
Kitson
R P
RP
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