From: Proceedings 10th World Congress of Cryosurgery
The clinical application of cryoimmunotherapy for advanced prostate cancer

November 1998
V Mouraviev, G Prochorov, V Konusova, A Simbircev, A Popovitch
Clinical Hospital of Russian Academy of Science, St. Petersburg, Russia

Introduction and Objectives: In an effort to enhance the T cells, several strategies have recently been explored aimed at creating therapeutic cancer vaccines. In case of tumor, as prostate cancer, for which the relevant tumor antigens are unknown, this approach has used the tumor cell itself as a source of antigen, modifying it in vitro to express immunomodulatory proteins such as cytokines. These studies have demonstrated in experiments that vaccination with tumor cells modified in this way frequently leads to the generation of systemic, tumor-specific immunity. In our opinion, the cryodestruction of prostate cancer may be an optimal model of so-called "specific autovaccination."

Methods: In an on-going pilot study, the standard palliative (single freezing) procedure of cryosurgical ablation of the prostate (CSAP) has been carried out in 5 patients with T4NI-3Ml (D2) stage and > 6 months follow-up. Before it during 1-2 days, we have injected subcutaneously the solution of recombinant interleucin- I -b in dose 40 ng/kg (produced by Scientific Institution of High Pure Bioproducts, St. Petersburg, Russia). In next day, after CSAP, additionally we have performed the intratumour injection of this agent (up to 10 ng). For enhancing of immune response, we have then continued this systemic immunotherapy during post-operative. Follow-up included the routine clinical investigation, prostatic specific antigen (PSA), x-rays and scintigraphy of skelet,

computer tomogpraphy and magnetic nuclear resonance imaging of abdominal and pelvic cavity, thorough immunomonitoring.

Results: In 3 cases, we have investigated the clinical remission of metastatic lesions, biochemical significant failure of PSA (from 83 to 125 ng/ml initially to 15-45 consequently), improvement of quality of life, indirect features of increasing of tumorspecific immunity (increasing of quantitative parameters of antigen activation- CD25, HLA-2, total lymphocytes, cytotoxic lymphocytes and natural killers; enhancing of functional activity of lymphocytes, stimulation of IL-2, IL-8, etc.). It was a very important event to support this specific immune response not by means of consequential cryotherapy, but the repeated immunotherapy by IL- I -b. In one case, we have reached the partial immune response with regression of some metastases from inner organs ( not osteolytic origin). In one case with terminal stage of D2, patient died due to the polyorgan failure and partially to the toxic complications of the intensive schema of cryochemo-immunotherapy.

Conclusion: Our initial results of pilot-study are encouraged about possible efficacy of this therapeutic modality for advanced prostate cancer. In comparing with previous studies, the enhancing of tumor-specific immunity may be achieved not at all by the consequential cryotherapy, but the repeated course of systemic immunotherapy by recombinant interleucin- I -b. But proving this fact, future investigations will be needed.

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