title: Ineffectiveness of adoptive chemoimmunotherapy with lymphokine-activated killer cells, interleukin-2, and cyclophosphamide on palpable intradermal murine bladder cancer.
abstract: The effects of adoptive immunotherapy with lymphokine-activated killer (LAK) cells and human recombinant interleukin 2 (IL2), on palpable intradermal (i.d.) bladder tumor were studied. The murine transitional cell carcinoma MBT-2 was used in C3H mice. IL2 was given intraperitoneally at 5,000 U/injection three times a day for 5 consecutive days beginning on day 10. LAK cells were generated in vitro from normal splenocytes: 10(7)-10(8) LAK cells were transferred intravenously on day 10 and, in some experiments, also on day 13. IL2 alone, LAK cells alone (total 8 x 10(7], and both in combination showed little or no influence on intradermally growing MBT-2 tumors. Cyclophosphamide was also combined with adoptive immunotherapy (IL2 and LAK). CY (100 mg/kg, i.p. on day 9 or 10) alone was able to suppress i.d. MBT-2 growth significantly. The combination treatment of IL2 and LAK cells with CY caused additional tumor growth suppression in a manner dependent on the total number of LAK cells transferred. The amount of the additional tumor growth suppression was, however, relatively small when compared with CY plus IL2-treated groups. In comparison, experimentally induced 3-day and 10-day pulmonary metastases of MBT-2 cells were treated by the same protocol of IL2 and LAK cells but without CY. IL2 alone reduced the number of gross metastatic nodules in the lung. The addition of LAK cells to the IL2 almost entirely eradicated the 3-day metastatic nodules but was less effective against the 10-day metastases. The data suggest that adoptive immunotherapy with IL2 and LAK cells mediates tumor regression of micrometastases at a selected organ (lung), but is ineffective against the same tumor growing in the skin or in gross metastatic nodules. Host immune suppression by CY was not beneficial in this model in creating a successful therapeutic effect of LAK cells and IL2.
authors.affiliation: Department of Urology, University of Rochester School of Medicine, NY 14642.
authors.forename: K
authors.initials: K
authors.lastname: Lee
authors.forename: R W
authors.initials: RW
authors.lastname: O'Donnell
authors.forename: A T
authors.initials: AT
authors.lastname: Cockett
mesh_terms: D000818:Animals; D002295:Carcinoma, Transitional Cell / Q000139:chemically induced / Q000628:therapy*; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000627:therapeutic use*; D004306:Dose-Response Relationship, Immunologic; D005260:Female; D007116:Immunization, Passive; D007167:Immunotherapy; D007376:Interleukin-2 / Q000627:therapeutic use*; D051379:Mice; D009374:Neoplasms, Experimental / Q000139:chemically induced; D011897:Random Allocation; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
chemical_list: D007376:Interleukin-2; D003520:Cyclophosphamide