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

A. Mazumder, T. J. Eberlein, E. A. Grimm, D. J. Wilson, A. M. Keenan, R. Aamodt, S. A. Rosenberg

Research output: Contribution to journalArticle

Abstract

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 x 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.

Original languageEnglish (US)
Pages (from-to)896-905
Number of pages10
JournalCancer
Volume53
Issue number4
StatePublished - 1984
Externally publishedYes

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Adoptive Immunotherapy
Lectins
Leukapheresis
Lymphocytes
Phytohemagglutinins
Neoplasms
Lung
Spleen
Erythrocyte Transfusion
Chills
Research Ethics Committees
Liver
Clinical Protocols
Embolism
Serum
Sarcoma
Thymidine
Nausea
Autoimmune Diseases
Cell Movement

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Mazumder, A., Eberlein, T. J., Grimm, E. A., Wilson, D. J., Keenan, A. M., Aamodt, R., & Rosenberg, S. A. (1984). Phase I study of the adoptive immunotherapy of human cancer with lectin activated autologous mononuclear cells. Cancer, 53(4), 896-905.

Phase I study of the adoptive immunotherapy of human cancer with lectin activated autologous mononuclear cells. / Mazumder, A.; Eberlein, T. J.; Grimm, E. A.; Wilson, D. J.; Keenan, A. M.; Aamodt, R.; Rosenberg, S. A.

In: Cancer, Vol. 53, No. 4, 1984, p. 896-905.

Research output: Contribution to journalArticle

Mazumder, A, Eberlein, TJ, Grimm, EA, Wilson, DJ, Keenan, AM, Aamodt, R & Rosenberg, SA 1984, 'Phase I study of the adoptive immunotherapy of human cancer with lectin activated autologous mononuclear cells', Cancer, vol. 53, no. 4, pp. 896-905.
Mazumder A, Eberlein TJ, Grimm EA, Wilson DJ, Keenan AM, Aamodt R et al. Phase I study of the adoptive immunotherapy of human cancer with lectin activated autologous mononuclear cells. Cancer. 1984;53(4):896-905.
Mazumder, A. ; Eberlein, T. J. ; Grimm, E. A. ; Wilson, D. J. ; Keenan, A. M. ; Aamodt, R. ; Rosenberg, S. A. / Phase I study of the adoptive immunotherapy of human cancer with lectin activated autologous mononuclear cells. In: Cancer. 1984 ; Vol. 53, No. 4. pp. 896-905.
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