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Systemic administration of autologous, alloactivated helper-enriched lymphocytes to patients with metastatic melanoma of the lung

A phase I study

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Summary

A phase I study was carried out to test the feasibility and toxicity of infusing large numbers of autologous, alloactivated helper lymphocytes into patients with metastatic melanoma. Patient peripheral blood lymphocytes (Pt-PBL) obtained by lymphopheresis and expressing the helper phenotype BT5/9 were separated and stimulated for 48 or 72 h with a pool of PBL from four to six healthy donors. Patients were then infused with such activated lymphocytes over a 2–3 h period. A total of 4 phereses and infusions (2/week for 2 weeks) were carried out for each cycle in each patient. Of the five patients treated, two received a second round of infusions. Infusion of autologous PBL stimulated in vitro for 48 h caused chills, fever, headache, and increased blood pressure. All symptoms disappeared in 2–3 h and were easily controlled by appropriate therapy. When lymphocytes were given after 72 h of allostimulation, no or very mild toxicity was observed. Serum chemistry, coagulation, autoimmunity, and urine analysis showed no gross abnormalities during therapy or follow-up of the patients. Immunological parameters (OKT4/OKT8 ratio, NK activity and cytotoxic T cell activity to autologous melanoma) were evaluated before starting the therapy, during its course and during the 3 to 6 months follow-up. The OKT4/OKT8 ratio increased significantly but transiently soon after the first course of infusions in one of the two patients tested. NK activity increased after 75–100 days in the three patients tested and in one of them it was high even after 180 days. No correlation between NK activity and prognosis was apparent. Cytotoxicity to autologous tumor was assessed in two patients, only one of whom exhibited an increased activity from 75 to 180 days, which was associated with a prognosis better than that of the negative patient. Five patients were treated: two had progressive disease, two had stable disease for 5 and 6 months, respectively. In the first of these patients, a new cycle of lymphocyte infusions was carried out which caused a measurable reduction of lung tumor nodules whose growth, however, resumed 4 months later. This patient died 14 months after the onset of therapy. The fifth patient had a partial regression of pulmonary and intracranial metastases after therapy, but eventually died 3 months later. These results indicate that infusion of a high numbers of autologous, allostimulated helper PBL is a feasible and safe procedure, which could therefore be used in future studies of adoptive immunotherapy of cancer.

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Authors and Affiliations

  1. Institute of Medical Microbiology, University of Milan, Italy

    Andrea Balsari

  2. Division of Surgical Oncology B, Istituto Nazionale per Studio e la Cura dei Tumori, Milan, Italy

    Raffaele Marolda & Natale Cascinelli

  3. Division of Experimental Oncology D, Istituto Nazionale per Studio e la Cura dei Tumori, Milan, Italy

    Carlo Gambacorti-Passerini, Gabriella Tona, Donatella Taramelli, Giuseppe Fossati & Giorgio Parmiani

  4. Blood Transfusion Service, Istituto Nazionale per Studio e la Cura dei Tumori, Milan, Italy

    Gianalfredo Sciorelli

  5. Institute of Biochemistry, University of Genoa, Italy

    Elisabetta Cosulich

  6. Present affiliation: Institute of General Pathology, University of Rome “La Sapienza”, Rome, Italy

    Donatella Taramelli

Authors
  1. Andrea Balsari
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  2. Raffaele Marolda
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  3. Carlo Gambacorti-Passerini
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  4. Gianalfredo Sciorelli
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  5. Gabriella Tona
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  6. Elisabetta Cosulich
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  7. Donatella Taramelli
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  8. Giuseppe Fossati
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  9. Giorgio Parmiani
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  10. Natale Cascinelli
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Balsari, A., Marolda, R., Gambacorti-Passerini, C. et al. Systemic administration of autologous, alloactivated helper-enriched lymphocytes to patients with metastatic melanoma of the lung. Cancer Immunol Immunother 21, 148–155 (1986). https://doi.org/10.1007/BF00199863

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  • DOI: https://doi.org/10.1007/BF00199863

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