Characteristics and uses of IL-2 in immunotherapy

Bolhuis, R. L. H.; Stoter, G.; Eggermont, Alexander

doi:10.1007/bf02170884

Cited by 3 publications

(1 citation statement)

References 31 publications

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“…Essentially, non-specific and non-MHC(major histocompatibility complex)-restricted killing of targets is mediated by natural killer (NK) cells, whereas T lymphocytes exert antigen-specific MHC-restricted cytotoxicity. Recent data suggest that NK cells may also exhibit allo-antigen-specific cytotoxicity [5] and that T lymphocytes can, upon IL-2 activation, display non specific and MHC-unrestricted cytolysis [6]. From the ex-213 periments we performed, using bulk PBL that contain both T lymphocytes and NK cells, the nature of the cytotoxic reaction could not be determined with certainty.…”

Section: Discussionmentioning

confidence: 99%

Possible role for cytotoxic lymphocytes in the pathogenesis of acute interstitial nephritis after recombinant interleukin-2 treatment for renal cell cancer

Vlasveld

Kemenade

Boer

et al. 1993

Cancer Immunol Immunother

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Abstract.A patient with renal cell cancer developed acute renal failure due to biopsy-proven acute tubulo-interstitial nephritis (AIN) in the 6th week of continuous infusion of 9 x 106 IU n r 2 day-1 recombinant interleukin-2 (rIL-2). We investigated whether the AIN was the result of a cellu lar cytotoxic reaction induced by the rIL-2 treatment. The cytolytic activity of cryopreserved peripheral blood lym phocytes (PBL), isolated before and at the end of the rIL-2 treatment (at the time of AIN), was studied after 5 days of culture with or without rIL-2 or anti-CD28 and immobi lized anti-CD3 antibodies. The PBL isolated before and at the end of the rIL-2 treatment showed cytolytic activity towards a number of allogeneic targets. However, only the PBL isolated at the end of the rIL-2 treatment showed, when stimulated with rIL-2 in vitro, significant cytolytic activity against an autologous renal cell line cultured from the AIN biopsy specimen and against an allogeneic renal cell cancer cell line. These PBL displayed no enhanced killing capacity towards autologous PBL and the melano ma cell line M14. These observations suggest that the AIN may be the result of a cytotoxic lymphocyte-mediated reac tion induced by the rIL-2 treatment.

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Section: Discussionmentioning

confidence: 99%

Possible role for cytotoxic lymphocytes in the pathogenesis of acute interstitial nephritis after recombinant interleukin-2 treatment for renal cell cancer

Vlasveld

Kemenade

Boer

et al. 1993

Cancer Immunol Immunother

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The role of cytokines in oncology

Lange¹,

Brugger²,

Rosenthal³

et al. 1991

The International Journal of Cell Cloning

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The availability of sufficient quantities of recombinant human cytokines and promising preclinical data have led to their introduction into clinical trials. Cytokines have potential as new therapeutic agents in a variety of hematological disorders as well as in solid tumors. Only a few of the still increasing number of these glycoprotein hormones have been studied in humans so far, either as single agents or in combination with chemotherapy and other cytokines. Their clinical effects, beneficial role in supportive care, and use in the treatment of certain cancer patients are reviewed.

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Clinical experience with the combined use of recombinant interleukin‐2 (IL2) and interferon alfa‐2a (IFNα) in metastatic melanoma

et al. 1991

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A multicentre study of IL2 and IFN alpha has been performed in 58 patients with metastatic melanoma. The scheme consisted of IL2 3.0 BRMP MU/m2/d as a continuous infusion for 4 d combined with subcutaneous administration of IFN alpha 6 MU/m2/d, day 1 + 4. The cycle was repeated every 2 weeks for a maximum duration of 26 weeks. 54 patients were evaluable for response. One (2%) achieved a complete and 10 (19%) a partial response. 19 (35%) patients were stable and 24 (44%) showed progressive disease. Common side-effects included fever, chills, fatigue, skin rash, anorexia, nausea and diarrhoea. Hypothyroidism was noted in 10% of the patients. These results show that this regimen of IL2 and IFN alpha is active but, in contrast to what could be expected, not superior to IL2 alone possibly due to suboptimal dosing. In an ongoing study in Rotterdam and Nijmegen, a more intense schedule was chosen, consisting of three daily i.v. doses of IL2 4.5 BRMP MU/m2 and IFN alpha 3.0 MU/m2 for 5 d. This regimen is repeated at intervals of 3 weeks for a total of three cycles. Presently, nine patients have been entered. One patient achieved a complete response, four a partial response (overall 56%), three had stable disease and one progressed. Toxicity was severe and treatment was prematurely stopped in five patients: myocardial infarction (one patient), atrial fibrillation (one patient), negative T waves and myocardial hypokinesia (one patient) and psychosis (two patients). This regimen can only be justified if the therapeutic results are superb, which has yet to be awaited.

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Characteristics and uses of IL-2 in immunotherapy

Cited by 3 publications

References 31 publications

Possible role for cytotoxic lymphocytes in the pathogenesis of acute interstitial nephritis after recombinant interleukin-2 treatment for renal cell cancer

Possible role for cytotoxic lymphocytes in the pathogenesis of acute interstitial nephritis after recombinant interleukin-2 treatment for renal cell cancer

The role of cytokines in oncology

Clinical experience with the combined use of recombinant interleukin‐2 (IL2) and interferon alfa‐2a (IFNα) in metastatic melanoma

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