Allogeneic gene-modified tumour cells in metastatic kidney cancer. Preliminary report.

An allogeneic irradiated RCC cell line, engineered to produce IL-2 (ACHN-IL-2), admixed with autologous metastatic formalin-treated tumour cells, was used to vaccinate ten MRCC patients in progression of disease in spite of IL-2 immunotherapy. The cells were administered subcutaneously and/or intra-tumourally. Sixty-four MRCC patients in progressive disease, not treated by vaccination but receiving similar IL-2 immunotherapy, were considered as the control group. Patients received 4-16 injections (mean 9 +/- 4), containing an average of 10.6 x 10(7) +/- 7.7 x 10(7) ACHN-IL-2-transfected cells (a minimum of 4 x 10(7), and a maximum of 31 x 10(7)). Four patients also received intra-tumour injections. Vaccination was administered during 30-418 days, and the follow-up continued for 649 +/- 353 days (190-1342). Throughout this period, the patients continued receiving the previously set immunotherapy treatment. No adverse side effects related to the treatment were observed. One complete and one partial tumour response were observed, as well as two stable and one no-relapse disease. All but one patient died. Responding patients resumed progression in 4-11 months and died 18 and 36 months after beginning the vaccine therapy. In spite of the small number of treated patients, Wilcoxon's test showed a significant (P < 0.05) improvement of the survival in the vaccinated group compared to that of the control. The described vaccination protocol seems safe, devoid of adverse side effects and promising. It warrants further investigation.

A preliminary report on the use of transfer factor for treating stage D3 hormone-unresponsive metastatic prostate cancer.

As conventional treatments are unsuccessful, the survival rate of stage D3 prostate cancer patients is poor. Reports have suggested the existence of humoral and cell-mediated immunity (CMI) against prostate cancer tumour-associated antigens (TAA). These observations prompted us to treat stage D3 prostate cancer patients with an in vitro produced transfer factor (TF) able to transfer, in vitro and in vivo, CMI against bladder and prostate TAA. Fifty patients entered this study and received one intramuscular injection of 2-5 units of specific TF monthly. Follow-up, ranging from 1 to 9 years, showed that complete remission was achieved in 2 patients, partial remission in 6, and no progression of metastatic disease in 14. The median survival was 126 weeks, higher than the survival rates reported in the literature for patients of the same stage.

Use of transfer factor for the treatment of recurrent non-bacterial female cystitis (NBRC): a preliminary report.

Results of conventional treatment of female non-bacterial recurrent cystitis (NBRC) are discouraging. Most patients show an unexpected high incidence of vaginal candidiasis, while their cell mediated immunity to Herpes simplex viruses (HSV) and Candida antigens seems impaired, and it is known that the persistence of mucocutaneous chronic candidiasis is mainly due to a selective defect of CMI to Candida antigens. Twenty nine women suffering of NBRC, and in whom previous treatment with antibiotics and non-steroid anti-inflammatory drugs was unsuccessful, underwent oral transfer factor (TF) therapy. TF specific to Candida and/or to HSV was administered bi-weekly for the first 2 weeks, and then once a week for the following 6 months. No side effects were observed during treatment. The total observation period of our cohort was 24379 days with 353 episodes of cystitis recorded and a cumulative relapse index (RI) of 43. The observation period during and after treatment was 13920 days with 108 relapses and a cumulative RI of 23 (P < 0.0001). It, thus, seems that specific TF may be capable of controlling NBRC and alleviate the symptoms.

Tumour regression after intralesional injection of interleukin 2 (IL-2) in bladder cancer. Preliminary report.

Six bladder cancer patients received intralesional injections by needle, under cystoscopic control, of 1969-4046 units (U) of xenogeneic IL-2 of high biological activity (324 U/ml; 397 micrograms/ml protein; 1.22 protein/U ratio). The treatment was spread over 7-54 days and 0.5 ml was injected each time. In 3/6 patients complete tumour regression was seen 43, 60 and 105 respectively days after the first IL-2 injection. In 2 a 70% regression was observed at days 45 and 75. In the last patient massive necrosis throughout the tumour mass was recorded on day 25 at radical cystectomy. In order to evaluate the minimum IL-2 U required to obtain positive clinical results and/or to assess whether the anti-tumour effect observed could be ascribed to the foreign protein of bovine origin contained in our IL-2 preparation, 4 additional bladder cancer patients were treated in 7-14 days with 156-1404 U of a second IL-2 lot with a much lower biological activity and similar protein content (52 U/ml; 289 micrograms/ml of protein; 5.55 protein/U ratio). No clinical or histological improvement was noted over a 42- to 54-day observation period. When we evaluated the 2 groups of patients by Student's t-test for both total U injected and U/kg of body weight (bw) we found a statistically significant differences (0.0025 less than p less than 0.0005 and p less than 0.0005, respectively). In contrast, no difference was seen for the injected protein amounts. The reported observations are in favour of a dose-dependent anti-tumour action mediated by IL-2 instead of foreign proteins. In none of the patients treated were any early or late adverse clinical side effects observed. Immunological monitoring (E, EAC, E-active rosettes, mitogen lymphocyte stimulations and leukocyte migration inhibition in the presence of allogeneic bladder cancer cells) performed on the peripheral blood (PB) showed significant but contrasting modifications after IL-2 injection. There was no clear correlation with the clinical course. The patients in whom we observed complete regression are still tumour free after 2, 4 and 7 months. In addition, in all the patients of the first group we observed an increase in tumour lymphoid infiltrate after IL-2 injection and in 2 patients lymphoid pseudo-follicles were also noted. In 2 of these patients we also observed scar-like areas in the place of the tumours previously seen.

Transitional cell carcinoma of the bladder. Differences between primary tumour and following relapses.

The presence of tumour-associated antigens in bladder carcinomas has been shown in leucocyte migration inhibition and lymphocyte stimulation using formalin-treated autologous tumour cells as antigen. The treatment of patients with an in vitro produced specific transfer factor enhances their reactivity in these tests. However, when tumour cells from relapses were substituted for those of the primary tumour, the reactivity previously observed was abolished. An antigenic modulation and/or a polymorphic expression of bladder tumour-associated antigens in secondary tumours is suggested and might be responsible for some immunological escapes.