Phase I study of the adoptive immunotherapy of human cancer with lectin activated autologous mononuclear cells

• Published in: Cancer 1984-02, Vol.53 (4), p.896-905
• Main Authors: Mazumder, Amitabha, Eberlein, Timothy J., Grimm, Elizabeth A., Wilson, Debra J., Keenan, Andrew M., Aamodt, Roger, Rosenberg, Steven A.
• Format: Article
• Language: English
• Subjects: Adult; Biological and medical sciences; Child; Evaluation Studies as Topic; Humans; Immunization, Passive; Immunomodulators; Indium; Lectins - pharmacology; Leukapheresis; Lymphocyte Activation; Lymphocytes - diagnostic imaging; Lymphocytes - immunology; Medical sciences; Middle Aged; Neoplasm Metastasis; Neoplasms - therapy; Pharmacology. Drug treatments; Radioisotopes; Radionuclide Imaging
• ISSN: 0008-543X; 1097-0142
• DOI: 10.1002/1097-0142(19840215)53:4<896::AID-CNCR2820530414>3.0.CO;2-E

In previous in vitro studies, the authors showed that phytohemagglutinin (PHA) stimulated peripheral blood lymphocytes (PBL) from cancer patients to generate cells that were lytic for fresh autologous tumor but not for lymphocytes or lymphoblasts. Thus, after IRB approval, a phase I clinical protocol was instituted in cancer patients who had failed all other therapy to determine the toxicity and effects, in vivo, of the infusion of large numbers of such PHA activated autologous PBL. Ten patients were treated on the protocol, six with sarcoma, one with melanoma, and three with colorectal cancer. Up to a total of 1.7 × 1011 PBL were obtained from 7 to 15 successive leukaphereses, the cells from each leukapheresis being incubated in vitro in medium containing PHA and human AB serum for 2 days and then reinfused following the next leukapheresis 2 days later. Toxicity encountered included fever and chills in 10/10 patients, headaches in 5/10, nausea and vomiting in 3/10, and requirement for erythrocyte transfusion in 8/10. No evidence for autoimmune disease, abnormal serum chemical or coagulation studies, or pulmonary emboli was found. 111Indium trafficking studies showed distribution of infused cells mainly to the spleen and liver, with some accumulation in the lungs and tumor especially after repeated infusions. In 9/10 patients, activated PBL were detected in the peripheral circulation by the sixth leukapheresis. Evidence for this was found by assaying the incorporation of tritiated thymidine (3H‐Tdr) into, and lysis of fresh tumor cells by, unstimulated PBL from successive leukaphereses. No tumor regression was seen in these patients with bulk disease. These studies demonstrated that large numbers of PHA‐activated PBL can be safely obtained and infused into humans, achieving an increase in the number of circulating activated cells with evidence of migration of cells to tumor, lungs, liver and spleen. Further studies of the use of activated lymphocyte infusion in conjunction with chemotherapy in humans are in progress.