Abstract
Immune RNA (I-RNA) is an RNA-rich nucleic acid preparation extracted from lymphoid cells or tissues following exposure to specific antigens in vitro or sensitization to specific antigens in vivo. It has been shown to induce normal, nonimmune lymphoid cells to mediate specific cellular and humoral immune responses in vitro and in vivo. Previous studies have demonstrated that I-RNA preparations extracted from the lymphoid organs of animals immunized with tumor cells mediate specific immune responses against tumor associated antigens in both animal models and human tumor systems. Based on this work, preliminary clinical trials of I-RNA immunotherapy were initiated 3 years ago. Cancer patients were treated with I-RNA extracted from the lymphoid organs of sheep immunized with either autologous tumor cells or allogeneic tumor cells of the same histologic type. I-RNA was administered weekly, intradermally, at doses of 4 to 8 mg/week without any significant local or systemic toxicity. The results of these preliminary trials suggest increased survival in patients with metastatic hypernephroma and possible benefit in the form of decreased recurrence rate in the adjuvant immunotherapy of patients with malignant melanoma. A prospectively randomized trial of adjuvant immunotherapy with I-RNA in patients with Dukes' classes B2 and C colorectal cancer has been recently undertaken.
Résumé
Le RNA immun (I-RNA) est une préparation d'acides nucléiques riche en RNA, extraite de cellules ou tissus lymphoÏdes préalablement exposés in vitro ou sensibilisés in vivo à des antigènes spécifiques. Il a été prouvé qu'il rend les cellules lymphoÏdes vierges capables de déclencher, in vitro et in vivo, des réponses immunologiques cellulaires et humorales spécifiques. Des travaux antérieurs ont démontré que des préparations d'I-RNA, extraites d'organes lymphoÏdes d'animaux immunisés par des cellules tumorales, sont capables de transférer, tant chez l'animal que chez l'homme, les réponses immunologiques spécifiques contre les antigènes associés aux tumeurs. A la suite de ces travaux, des essais cliniques préliminaires d'immunothérapie par l'I-RNA ont été entamées il y a 3 ans. Des malades atteints de cancer ont été traités avec du I-RNA extrait d'organes lymphoÏdes de moutons immunisés avec des cellules tumorales, autologues ou homologues, de mÊme type histologique. L'I-RNA a été administré par voie intradermique, à la dose de 4–8 mgr/semaine, sans aucun effet toxique local ou systémique. Les résultats de ces études préliminaires semblent indiquer une prolongation de la survie dans des cas d'hypernéphrome avec metastases et un effet bénéfique (réduction de la fréquence des récidives) lorsque l'I-RNA est utilisé comme immunothérapie adjuvante en cas de mélanome malin. Récemment, une étude prospective randomisée a été entreprise avec I-RNA comme immunothérapie adjuvante dans des cas de cancer du colon et du rectum aux stades Dukes B2 et C.
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Supported in part by grants number CA-21664, CA-12582, C A-16402, and NIH-4-444992-32691 from the National Institutes of Health and by grant number 1797-03 from the Veterans Administration.
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Dekernion, J.B., Ramming, K.P. & Pilch, Y.H. Immunotherapy of human malignancies with immune RNA. World J. Surg. 1, 625–635 (1977). https://doi.org/10.1007/BF01556192
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DOI: https://doi.org/10.1007/BF01556192