Phase I Clinical Studies With Lymphoblastoid Lymphokine Preparations From the Rpmi 1788 Cell Line

Rodes, Ned D.; McEntire, John E.; Dunn, P.A.; Decker, Miriam; Kardinal, Carl G.; Gilliland, C. Dean; Oxenhandler, Ronald W.; Papermaster, Ben W.

doi:10.1016/b978-0-12-406080-7.50061-8

Cited by 3 publications

(1 citation statement)

References 26 publications

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“…With some of the in vitro produced mediators like interferons or interleukins, therapeutic assays have been carried out already in vivo (6,8,10,23). Some of the most interesting results have been: tumour growth reduction (1 7,27), improvement of immune deficiency by substitution of externally produced mediators (19, 25) and aspects of therapeutic application in parasitic, bacterial and fungal infections (4,12,20,26).…”

Section: Introductionmentioning

confidence: 99%

Enhancement of Non‐Specific Antiviral Defence Mechanisms in NMRI‐Mice by Cell Culture Mediators

Reubel

Büttner

Mayr

1986

Journal of Veterinary Medicine, Series B

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Summary Through in vitro stimulation of different cell types with various stimulating substances, production of mediators with antiviral activity in vivo was studied. In two lethal virus mouse challenge models — adult NMRI‐mice challenged with pseudorabies virus (PRV) and baby mice challenged with stomatitis vesicularis virus (VSV) — antiviral efficacy of cell culture supernatants (CCSs) was demonstrated. In a plaque reduction assay, interferon activity in CCSs and in serum of CCS‐treated mice was investigated. Prophylactic treatment with CCSs from murine hybridomas and human lymphomas — stimulated by inactivated parapoxvirus ovis — reduced the mortality rate of challenged mice significantly. None of the cell cultures secreted interferon into the medium, whereas intraperitoneal application of some CCSs induced interferon activity in serum of mice. A possibility for production of non‐antigen‐specific mediators was shown by appropriate stimulation of certain cell types in vitro. Prophylactic treatment with these mediators triggered non‐specific defence mechanisms in mice against two lethal virus infections. Zusammenfassung Steigerung der unspezifischen Virusabwehr bei NMRI‐Mäusen durch Mediatoren aus Zellkulturen Mit verschiedenen Stimulationssubstanzen wurde versucht, in vitro unterschiedliche Zellarten zur Sekretion von Mediatoren mit antiviraler Wirksamkeit in vivo anzuregen. Die Prüfung der antiviralen Wirksamkeit der Zellkulturüberstände (ZKÜ) erfolgte in zwei Virusbelastungsmodellen, wobei adulte NMRI‐Mäuse mit Aujeszky‐Virus und juvenile Mäuse mit Vesicularis Stomatitis‐Virus belastet wurden. Mit einem Plaque‐Reduktions‐Test wurde die Interferon (IFN)‐Aktivität in einigen ZKÜ und im Serum ZKÜ‐behandelter Tiere bestimmt. Vorbeugende Behandlung mit ZKÜ aus murinen Hybridomas bzw. humanen Lymphomas, die mit inaktiviertem Parapoxvirus ovis stimuliert waren, verringerte die Mortalitätsrate von virusbelasteten Mäusen erheblich. Keine der Zellkulturen sezernierte IFN in den Überstand, während die intraperitoneale Verabreichung einiger ZKÜ IFN‐Aktivität im Serum der Mäuse induzierte. Die Versuche zeigen die Möglichkeit auf, bestimmte Zellarten mit geeigneten Stimulationssubstanzen zur Sekretion von Mediatoren anzuregen, mit denen sich bei Mäusen in vivo die unspezifische Infektabwehr gegen bestimmte Virusinfektionen erhöhen läßt.

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Section: Introductionmentioning

confidence: 99%

Enhancement of Non‐Specific Antiviral Defence Mechanisms in NMRI‐Mice by Cell Culture Mediators

Reubel

Büttner

Mayr

1986

Journal of Veterinary Medicine, Series B

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The Response of Tumor-Bearing Patients to the Injection of Lymphoid Cell Line Lymphokine

Dumonde

Pulley

Hamblin

et al. 1984

Thymic Hormones and Lymphokines

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Immunostimulation

Drews

1984

Klin Wochenschr

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Three classes of immunostimulating drugs are described, each representing a different approach to the problem of pharmacological immunostimulation. The rationale for the use of microbes or microbial agents as immunostimulators rests on the fact that some micro-organisms, especially those that replicate intracellularly, carry a special potential to activate macrophages. Clinically, the use of these agents in patients with tumors and infections has been disappointing; however, there have been positive exceptions like the responsiveness of melanomas and bladder carcinomas to the injection of BCG. Many of the inconclusive results may be due to insecurities in the dosage of microbial preparations and to a general lack in standardization. Some structures with high efficacy and low toxicity which have recently evolved from this field deserve further investigation. A number of structurally unrelated synthetic compounds was found to influence immune parameters. Levamisole can today be classified as an immunostimulating drug with limited utility in recurring infections and in chronic polyarthritis. Several immunostimulating drugs which have attracted interest contain a purine as the effective component. This is not surprising in view of the fact that many genetically determined immunodeficiencies can be traced to defects of enzymes which play a crucial role in purine biosynthesis. Finally, the potential role of lymphokines as stimulators of the immunosystem is briefly described. Some of these glycoproteins have recently become available for clinical trials. Others will be made available through genetic engineering. The therapeutic utility of these compounds is not yet clear; they will, however, be of great value as probes for the study of immune functions and for the development of immunopharmacology.

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Phase I Clinical Studies With Lymphoblastoid Lymphokine Preparations From the Rpmi 1788 Cell Line

Cited by 3 publications

References 26 publications

Enhancement of Non‐Specific Antiviral Defence Mechanisms in NMRI‐Mice by Cell Culture Mediators

Enhancement of Non‐Specific Antiviral Defence Mechanisms in NMRI‐Mice by Cell Culture Mediators

The Response of Tumor-Bearing Patients to the Injection of Lymphoid Cell Line Lymphokine

Immunostimulation

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