Recombinant interleukin-2 inhibits growth of human tumor xenografts in congenitally athymic mice

Bubenı́k, Jan; Kieler, J; Tromholt, V.; Indrová, M; Lotzová, Eva

doi:10.1016/0165-2478(87)90013-7

Cited by 8 publications

(1 citation statement)

References 14 publications

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“…Peritumoral injections of natural or recombinant IL-2 as sole therapeutic agent, however, has been shown to reduce tumor in animal models [29,59,60]. Xenografts of human carcinoma lines growing in nude mice were also inhibited with local, peritumoral rlL-2 administration [61]. Plunkett and co-workers showed that 90% of 51Chromium-labelled rat LAK cells remained viable at least one hour following stereotaxic implantion into brains of syngeneic hosts [62].…”

Section: Clinical Trials Of Ril-2 Plus Activated Lymphocytes For Gliomamentioning

confidence: 99%

Immunotherapy for malignant glioma using human recombinant interleukin-2 and activated autologous lymphocytes

1990

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Over the past few years, we and a number of other groups have conducted laboratory experiments and clinical trials of human recombinant interleukin-2 (rIL-2) alone or in combination with autologous 'activated' lymphocytes expressing in vitro tumoricidal activity in order to define toxicity and indicate its potential efficacy in patients with high-grade glioma. Because high rIL-2 concentrations can be attained with considerably less toxicity than with a systemic approach, all of the clinical trials, to date, have chosen a direct route; injecting lymphokine and cells into tumor tissue, the cystic cavity remaining after tumor excision, and/or neural parenchyma surrounding the site of tumor excision. While the rIL-2 therapies, as they have been applied in animal glioma models and patients, are safe, cerebral edema around the site of treatment has been a consistent finding. We have also seen, however, that steroid medications used by patients to control their cerebral edema may depress the anti-tumor activity of rIL-2 by depressing the capacity of lymphocytes to develop normal LAK activity. Although none of the immunotherapies involving rIL-2 have produced cures, the fact that sustained clinical responses have been reported, suggests that such therapies may slow a recurrence of tumor at the site of treatment. Efforts to improve outcome from rIL-2--based immunotherapies for malignant glioma are continuing with manipulation of rIL-2 dosing and scheduling and also with combinations of rIL-2 and other recombinant cytokines.

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Section: Clinical Trials Of Ril-2 Plus Activated Lymphocytes For Gliomamentioning

confidence: 99%

Immunotherapy for malignant glioma using human recombinant interleukin-2 and activated autologous lymphocytes

1990

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Growth and Cell Proliferation of Human Renal Cell Carcinomas Xenografted into BALB/c nu/nu Mice

Harasim

Loer

Wirth

et al. 1989

Investigative Urology 3

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In vivo system to detect long-term continuous release of bioactive interleukin-2 by immunopharmacological depot preparations in nude mice with human tumors

Huland

Falk

Hübner

et al. 1995

J Cancer Res Clin Oncol

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For continuous release of cytokines for local application at tumor sites, we developed depot preparations consisting of a carrier substance (ethylene vinyl acetate copolymer) and either natural interleukin-2 (nIL-2) at 5 x 10(5) BRMP U or natural interferon-alpha (nIFN alpha) at 3 x 10(5) IU. We transplanted human tumors in nude mice and placed depot preparations next to the tumors to confirm the in vivo long-term biological activity of the depots according to the ability of IL-2 to inhibit growth of the tumors. Five different human tumors were used. Mice with each tumor were divided into groups of six to eight receiving different treatments: control (no treatment), human serum albumin, but no cytokine, IL-2 depot, IFN alpha depot and IFN alpha plus IL-2 depot. After proven in vivo tumor growth, these depot preparations were implanted subcutaneously directly at the tumor sites. Tumor growth was significantly reduced by IL-2 and IFN alpha plus IL-2 for 3 weeks after depot implantation. Complete tumor remission was not achieved. IFN alpha alone did not influence tumor growth. Our data show that the nude mouse is a valuable model for testing biological activity and release time of IL-2 depot preparations in vivo.

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Recombinant interleukin-2 inhibits growth of human tumor xenografts in congenitally athymic mice

Cited by 8 publications

References 14 publications

Immunotherapy for malignant glioma using human recombinant interleukin-2 and activated autologous lymphocytes

Immunotherapy for malignant glioma using human recombinant interleukin-2 and activated autologous lymphocytes

Growth and Cell Proliferation of Human Renal Cell Carcinomas Xenografted into BALB/c nu/nu Mice

In vivo system to detect long-term continuous release of bioactive interleukin-2 by immunopharmacological depot preparations in nude mice with human tumors

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