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Immunotherapy of cancer with thymosin

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Abstract

Bovine thymosin fraction 5, a partially purified thymic extract, has been employed in phase I and phase II clinical studies in immunodeficient cancer patients. Some improvement in cell-mediated immune functional parameters has been seen, notably an increase in percentages of peripheral blood T lymphocytes as detected by rosette formation with sheep erythrocytes. Thymosin-induced rosette-forming cell increases demonstrated in vitro prior to the institution of thymosin treatment generally were predictive of those patients who showed the in vivo rise in circulating T cells following thymosin administration. Although some patients exhibited clinical improvement, it is still too early to infer from these open studies whether or not these improvements can be attributed to thymosin treatment. Well-controlled randomized trials are in progress to objectively examine the clinical efficacy of thymosin fraction 5 therapy in cancer patients.

Thymosin fraction 5 contains several thymus-specific polypeptides which appear to act on lymphoid cells at a number of stages during their differentiation. Several of these individual polypeptides have been isolated, and one has been sequenced (thymosinα 1) and found to have immunoenhancing activity. Cancer patients may be viewed in many cases as exhibiting an “acquired” disease-related or treatment-related deficiency in cell-mediated immunity. This may render immunotherapeutic manipulations nonbeneficial and may in fact contribute to tumor progression and/or metastasis. By treating such patients with thymosin fraction 5 or the specific polypeptide(s) within fraction 5 required to allow the appearance of immunocompetent T lymphocytes, these patients may become amenable to immunotherapy, more resistant to infection with opportunistic organisms, and perhaps may develop endogenous antitumor defenses.

Résumé

La fraction 5 de la thymosine bovine, un extrait thymique partiellement purifié, a été utilisée dans des études cliniques (phases I et II) chez des cancéreux présentant des déficits immunitaires. Nous avons observé des améliorations de certains caractères fonctionnels d'immunité cellulaire, entre autres des augmentations de pourcentages de lymphocytes T dans le sang périphérique (mesuré par la formation de rosettes en présence de globules rouges de mouton). En général, l'observation in vitro, sous l'effet de la thymosine, d'une augmentation du nombre de cellules génératrices de rosettes, permet de prédire l'effet thérapeutique in vivo: les mÊmes malades voient, après administration de thymosine, s'élever leur nombre de cellules T circulantes. Bien que nous ayons constaté certaines améliorations cliniques, il est trop tÔt pour affirmer, sur la base de ces quelques essais, que c'est bien la thymosine qui a amélioré l'état des malades. Des études randomisées et contrÔlées sont en cours pour préciser ces premières appréciations.

La fraction 5 de la thymosine contient des polypeptides spécifiques thymiques qui paraissent agir sur certains stades de la différenciation des lymphocytes. Plusieurs de ces polypeptides ont été isolés dans la fraction 5. L'un d'entre eux (thymosineα 1) a une activité immunostimulante in vitro. On a pu déterminer la séquence d'acides aminés qui le composent. On peut admettre que de nombreux malades atteints de cancer présentent un déficit de l'immunité cellulaire, dépendant de la maladie ou du traitement. A cause de ce désordre, certaines thérapeutiques à visée immunologique peuvent Être délétères: elles peuvent favoriser la croissance et/ou la dissémination de la tumeur. En traitant ces patients avec la fraction 5 ou avec son (ou ses) polypeptide(s) spécifiques qui stimulent la formation de lymphocytes T immunocompétents, on peut espérer qu'ils deviendront justiciables d'une immunothérapie, qu'ils seront plus résistants aux infections occasionnelles et qu'ils développeront mÊme peut-Être des mécanismes endogènes de défense anticancéreuse.

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  1. Division of Biochemistry, Department of Human Biological Chemistry and Genetics, University of Texas Medicalranch, Galveston, Texas, USA

    Jeffrey L. Rossio Ph.d. & Allan L. Goldstein Ph.d.

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  1. Jeffrey L. Rossio Ph.d.
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  2. Allan L. Goldstein Ph.d.
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Supported in part by National Cancer Institute Grants CA14108 and CA16964, The John A Hartford Foundation, Inc., and Hoffmann-La Roche, Inc., Nutley, New Jersey.

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Rossio, J.L., Goldstein, A.L. Immunotherapy of cancer with thymosin. World J. Surg. 1, 605–613 (1977). https://doi.org/10.1007/BF01556187

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