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Immunological evaluation of patients with hematological malignancies receiving ambulatory cytokine-mediated immunotherapy with recombinant human interferon-α2a and interleukin-2

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Summary

Immunological parameters were evaluated in patients treated with cytokine-mediated immunotherapy (CMI) consisting of low doses of recombinant human interferon α2a (rIFNα) and recombinant human interleukin-2 (rIL-2) administered either concomitantly or sequentially by subcutaneous self-injections in an outpatient setting. Twenty-six patients with hematological malignancies and 2 metastatic melanoma patients in a progressive stage were enrolled in this clinical trial. Of the 26 patients, 24 were at a stage of minimal residual disease, including 14 patients who had received autologous bone marrow transplantation (ABMT) 2–5 months previously, 7 chronic myelogenous leukemia (CML) and 3 acute myeloid leukemia (AML) patients. Two patients (1 CML and 1 mult. myeloma) were treated at a stage of progressive disease. Non-MHC-restricted cytotoxicity directed against natural-killer(NK)-resistant (Daudi) and NK-sensitive (K562) target cells was assessed before, during and after CMI, either in fresh peripheral blood samples (spontaneous activity) or after in vitro rIL-2 activation (induced activity). Spontaneous killing activity was low prior to treatment, but increased upon termination of treatment in 10/15 evaluated cycels. rIL-2-activated cytotoxicity in vitro was markedly elevated in 8/12 and 6/8 patients after one and two cycles, respectively, of sequential treatment, as well as in 3/8 CML and 5/6 patients after one and two cycles, respectively, of concomitant treatment Activation of the T cell mitogenic response was demonstrated in 6/9 patients after concomitant CMI, while no such effect was observed throughout a sequential treatment in lymphoma and leukemia patients after ABMT. Although a direct correlation between immune stimulation and the in vivo antitumor response cannot yet be determined, our clinical observations support a beneficial therapeutic effect in a substantial number of patients. These results indicated that the ambulatory CMI protocol of rIL-2 and rIFNα could stimulate the host defense immune system and may be helpful in mediating the in vivo antitumor response in patients with minimal residual disease.

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  1. Menahem Ben Shahar

    Present address: Department of Oncology, Rambam Medical Center, Haifa, Israel

Authors and Affiliations

  1. The Department of Bone Marrow Transplantation and Cancer Immunobiology Research Laboratory, Hadassah University Hospital, 91 120, Jerusalem, Israel

    Shoshana Morecki, Shoshana Revel-Vilk, Corinne Nabet, Marjorie Pick, Aliza Ackerstein, Arnon Nagler, Elizabeth Naparstek, Menahem Ben Shahar & Shimon Slavin

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  1. Shoshana Morecki
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Morecki, S., Revel-Vilk, S., Nabet, C. et al. Immunological evaluation of patients with hematological malignancies receiving ambulatory cytokine-mediated immunotherapy with recombinant human interferon-α2a and interleukin-2. Cancer Immunol Immunother 35, 401–411 (1992). https://doi.org/10.1007/BF01789019

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