Allogeneic Gene-Modified Tumour Cells in Metastatic Kidney Cancer. Preliminary Report

Pizza, Giancarlo; De Vinci, C.; Lo Conte, G.; Mazzuca, A.; Corrado, G.; Menniti, D.; Benati, A.; Romagnoli, P.; Fornarola, V.; Busutti, L.; Palareti, A.; Capanna, R.; Di Maio, V.; Ratini, S.; Gulino, A.; Vacca, A.; Melchiorri, L.; Ferrari, M.; Boriani, S.; Baricordi, R. O.

doi:10.14712/fb2003049040147

Fol. Biol. 2003, 49, 147-159

https://doi.org/10.14712/fb2003049040147

Allogeneic Gene-Modified Tumour Cells in Metastatic Kidney Cancer. Preliminary Report

Giancarlo Pizza¹, C. De Vinci¹, G. Lo Conte¹, A. Mazzuca¹, G. Corrado¹, D. Menniti¹, A. Benati¹, P. Romagnoli¹, V. Fornarola¹, L. Busutti², A. Palareti³, R. Capanna⁴, V. Di Maio¹, S. Ratini¹, A. Gulino⁵, A. Vacca⁵, L. Melchiorri⁶, M. Ferrari⁷, S. Boriani⁸, R. O. Baricordi⁶

¹Immunotherapy Module, Operative Unit of Urology, Department of Urology and Nephrology, S. Orsola-Malpighi Hospital, Bologna, Italy
²Operative Unit of Radiotherapy, Department of Oncology, S. Orsola-Malpighi Hospital, Bologna, Italy
³Department of Computer Science, University of Bologna, Bologna, Italy
⁴2nd Division of Orthopaedics and Reconstructive Surgery Centre, Florence, Italy
⁵Experimental Medicine, University "La Sapienza", Roma, Italy
⁶Department of Experimental and Diagnostic Medicine, Section of Medical Genetics, University of Ferrara, Ferrara, Italy
⁷Experimental Institute of Zoo-prophylaxis, Emilia-Romagna and Lombardia Regions, Brescia, Italy
⁸Operative Unit of Orthopaedics, Maggiore Hospital, Bologna, Italy

Received May 2003
Accepted May 2003

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 intratumourally. 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 10⁷ ± 7.7 x 10⁷ ACHN-IL-2transfected cells (a minimum of 4 x 10⁷, and a maximum of 31 x 10⁷). 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, Wilcoxonís 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.