Prospects for cryo-immunotherapy in cases of metastasizing carcinoma of the prostate

doi:10.1016/0011-2240(71)90050-2

Cryobiology

Volume 8, Issue 3, June 1971, Pages 271-279

https://doi.org/10.1016/0011-2240(71)90050-2 Get rights and content

Abstract

Clinical observations of the remission of metastatic lesions in six patients following cryothermic treatment of their primary prostatic tumor suggest that factors other than freezing may be involved in both primary and secondary cellular destruction. The precise mechanism(s) operative in the cases presented is not yet definitive; however; priliminary data are suggestive of immunologic factors. The nature of the possible immunologic process underlying these remissions is discussed.

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It can be assumed that the use of anticancer cryovaccines containing cancer stem cell proteins (glycoproteins) will lead to their eradication through the activation of a specific cell and humoral immune response to certain immunogenic sites on these cells and, therefore, to an increased probability of curing cancer. Studies demonstrating the complete disappearance of metastatic nodes after cryosurgery performed in primary tumors indirectly support this notion [3,116,117]. A retrospective analysis of the above results, as well as the observations of prostatic carcinoma described in Refs. [2,32], is of particular interest from the point of view that the findings indicate a less pronounced therapeutic effect of cryosurgery during operations on late-stage tumors than on early-stage.
Autologous and allogeneic cryoimmunological medicine is a brand new branch of biomedical science and clinical practice that examines the features and formation of the immune response to immunogenic properties of normal and malignant biological structures altered by ultralow temperature, as well as specific changes in the structural and functional characteristics of immune cells and tissues after cryopreservation. Cryogenic protein denaturation phenomenon provides important insights into the mechanisms underlying the damage to cryogenic lesions immediately after freeze–thawing sessions in bioscience and medicine applications. The newly formed cryocoagulated protein components (cryomodified protein components) are crucial in cryoimmunology from the perspective of the formation of immunological substances at ultralow temperatures. Dendritic cells and cryocell detritus (cryocell debris) formed in living biological tissue after exposure to ultralow temperature in vivo may be an indication of one of the essential mechanisms involved in the cryoimmunological response of living structures to the impact of ultralow temperature exposure. Hence, the formation of new autologous and allogeneic cryoinduced immunogenic substances is a novel concept in biomedical research globally. Accordingly, this review focuses on issues concerning the peculiarities of the interaction of the immune system with a dominant malignant neoplasm tissue after exposure to subzero temperatures, considering the original cryogenic technical approaches. We present an overview of the state-of-the-art methods of cryoimmunology, and their major developments, past and present. The need for the delineation of structural and functional characteristics of the biological substrates of the immune system after cryopreservation that can be used in adoptive cell therapy, especially in cancer patients, is emphasized.
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The tumor antigens released from the necrotic tumor cells in tumor-bearing grafted bone inside the cage activate the tumor-specific immune response. Previous reports have suggested immune system activation brought about by cryosurgery [4,5,8,9]. Nishida et al. [10] reported that reimplantation of tumor tissue frozen using liquid nitrogen induces antitumor activity against murine osteosarcoma and the serum levels of INF-γ and IL-12 increased after treatment [11].
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The sample consisted of 65 consecutive patients who underwent second-generation TES.
Interferon gamma (IFN-γ) and interleukin-12 (IL-12) before surgery and at both 1 and 3 months after surgery was used to assess the immunity-enhancing effect.
In second-generation TES, instead of harvesting autograft from the ilium or fibula, the resected lamina and vertebral body from TES are frozen using liquid nitrogen and used as grafted bone for spinal reconstruction. In the most recent 33 of the 65 cases, in addition to the TES procedure, a small amount of the tumor tissue from the resected tumor-bearing vertebra was also placed into liquid nitrogen. This small amount of tumor tissue was then implanted subcutaneously on one side of the axilla at the end of the TES surgery. In 60 of 65 cases, measurement of IFN-γ and IL-12 was performed.
IFN-γ increased after surgery in 45 (75%) of 60 cases. The mean IFN-γ relative concentrations at both 1 and 3 months after surgery, as compared with before surgery, were significantly higher (284%±596% and 275%±354%: p<.05). IL-12 increased after surgery in 44 (73.3%) of 60 cases. The mean IL-12 relative concentrations at both 1 and 3 months after surgery, as compared with before surgery, were significantly higher (277%±385% and 486%±1032%: p>.05 and p<.01) at 3 months. At final follow-up, 13 of the 65 patients died due to progression of metastases (mean 12.6 months after TES), 15 remained free from disease, and 36 patients were alive with disease.
The second-generation TES using frozen tumor-bearing autograft inside a cage affords three benefits: (1) no pain at the bone harvest site, (2) shortening of operation time, and (3) decrease of blood loss. Moreover, our results show that second-generation TES provides not only a local radical cure but also a systemic immunological enhancement.
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^☆: Supported by a grant from the John A. Hartford Foundation, Inc.

²: Present address: Immunology Section, Renal Unit, Memorial Hospital of Springfield, Springfield, Illinois.

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Prospects for cryo-immunotherapy in cases of metastasizing carcinoma of the prostate☆

Abstract

J. Urol

Advan. Immunol

Eur. J. Cancer

Immunology and the prostate

A possible immuno-cryothermic response in prostatic cancer

Fluorescent studies of antibodies to rabbit male urogenital tissue

Experientia

Precipitating antibody in the sera of patients treated cryosurgically for carcinoma of the prostate

Exp. Med. Surg