Intralesional sonographically guided injections of lymphokine-activated killer cells and recombinant interleukin-2 for the treatment of liver tumors: a pilot study.

Primary and metastatic liver cancers have a poor prognosis. At present, sonographically guided alcohol injection results in a partial reduction of cancer masses even if severe toxic effects (including pain and bleeding) are always present. For these reasons, a pilot study was started to evaluate the feasibility of an intralesional adoptive immunotherapeutic approach, using lymphokine-activated killer (LAK) cells and recombinant interleukin-2 (rIL-2). Nine patients (one with primary hepatocarcinoma and eight with liver metastases) entered the study. Four cycles of weekly injections of LAK cells (ranging from 2 to 9 x 10(8)) and 10(6) IU rIL-2 were performed percutaneously under ultrasonic guidance. In the same period, 3 x 10(6) IU rIL-2/day, for 24 days, was injected subcutaneously. All patients but one completed the therapy. Side effects were limited to grade 1-2 fever and were mostly related to rIL-2 subcutaneous injections. No patients complained of having pain during intralesional therapy. Two complete responses were detected. One partial response, four stable diseases, and one progressive disease were observed. One patient was not evaluable. These preliminary results suggest that sonographically guided intralesional adoptive immunotherapy of liver tumors is feasible, safe, and could offer promising therapeutic advantages in cancers for which conventional treatment is generally unsatisfactory.

Cytotoxic effects of high energy shock waves on cancer cells linked to metallic beads vehicled by monoclonal antibodies.

Previous studies have reported that high energy shock waves (HESW), generated by an electrohydraulic lithotriptor, may have some utility as a cancer treatment modality. Furthermore, it has been described that shock waves propagating in a fluid, show demolitive effects at the level of the interface of a solid fragment immersed in the fluid. In this study, we demonstrate that it is possible to enhance the antineoplastic effects of HESW if treated cells or tissues are linked to monoclonal antibodies (MoAbs) conjugated with metallic beads (MB) (about 1 mu of diameter) and specific for a cancer cell surface determinant. A leukemic cell line was used to study the effects of HESW on cells linked to MB. A fresh human breast cancer specimen was used to perform the assay on tumor tissue. MB linked treated cell viability, growth curve, cloning efficiency and Bromodeoxyuridine incorporation were reduced in comparison to cells treated with HESW alone. Our data suggest that the presence of solid fragments vehicled by MoAbs on a cancer cell surface is able to synergize with the limited antineoplastic effects of HESW.

Treatment of superficial bladder cancer with intravesical perfusion of rIL-2: a follow-up study.

We have recently reported the results of a phase I study on the intravesical perfusion of recombinant interleukin-2 in patients with superficial bladder cancer. The treatment feasible with mild toxic effects, especially compared with the treatment using TUR and instillations of Bacillus Calmette-Guerin. The follow-up of these phase I study patients was continued for another twelve months. During this period, cytoscopy and cytological examination of cells washed from bladder were performed every four months. The results showed that three out of 9 patients relapsed, over a period ranging from 6 to 20 months after treatment. All these data clearly confirm that the intravesical perfusion of rIL-2 is feasible, safe and should be an effective and nontoxic treatment of patients with superficial bladder cancer.

Selective expansion of circulating CD8+ lymphocytes during cancer immunotherapy with interleukin-2 plus alpha-interferon but not with interleukin-2 alone.

The use of interferons in anti-cancer therapy is justified by the experimental evidence that these cytokines are able to enhance in vitro the expression of some surface molecules such as major histocompatibility complex and tumor associated lymphocytes. Furthermore, a synergism of action of interleukin-2 with alpha-interferon in the treatment of human malignancies has been described. Nevertheless, whether the in vivo role of interferons associated to interleukin-2 as anti-cancer drugs is actually related to the properties of this cytokine of modulating surface molecule expression on target cells, has never been clearly reported. In this report, we describe an immune system cell resetting, during immunotherapy with interleukin-2 plus alpha-interferon, which seems to support this hypothesis.

A phase I study of intravesical continuous perfusion of recombinant interleukin-2 in patients with superficial bladder cancer.

A Phase I study was started to evaluate the locoregional and/or systemic toxic effects of the continuous perfusion of recombinant interleukin-2 (rIL-2) in superficial bladder cancer. Three different dose levels were used: 3 x 10(6) IU/day (3 patients), 9 x 10(6) IU/day (3 patients) and 27 x 10(6) IU/day (3 patients). Two patients (one treated with 3 x 10(6) and another with 27 x 10(6) IU/day of rIL-2) had hematuria after the end of the treatment, one patient had fever (grade I) and 7 of 9 patients experienced hypotension (grade I-II). All effects were not dose related. Routine laboratory tests indicated that no significant variations of biochemical parameters occurred. A phenotypic analysis of white blood cells detectable in the bladder, showed an evident locoregional activation of lymphoid cells. In particular, T lymphocytes expressed activation antigens (such as CD25 and HLA-DR) following treatment with rIL-2. A 6- to 12-month clinical follow-up, showed that all patients but one (which recurred after 5 months) are alive and disease-free. This therefore indicates that the locoregional perfusion of rIL-2 is safe and gives clinical results similar to those obtained using Calmette-Guérin bacillus locoregional instillation, in patients who underwent a transurethral resection of superficial bladder cancer.