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Immunosuppressive Effects of L-Asparaginase¹

Department of Developmental Therapeutics, The University of Texas M. D. Anderson Hospital and Tumor Institute at Houston, Houston, Texas 77025

The immunological effects of L-asparaginase were studied in man. L-Asparaginase suppressed the development of delayed hypersensitivity to primary antigens in cancer patients receiving therapeutic doses of the drug. The development of delayed hypersensitivity skin reactions was completely or partially suppressed in 5 out of 8 patients immunized with 2 mg keyhole limpet hemocyanin and in 5 out of 6 patients immunized with a synthetic amino acid copolymer of glutamic acid, lysine, alanine, and tyrosine. L-asparaginase did not change established delayed hypersensitivity skin reactivity.

Production of antibodies to keyhole limpet hemocyanin was delayed and suppressed by L-asparaginase and 3 out of 8 patients did not produce any antibody to this antigen. Antibody production was delayed and antibody titers were lower compared to controls in the other 5. Production of antibodies to the synthetic amino acid copolymer of glutamic acid, lysine, alanine, and tyrosine was delayed by treatment.

Lymphocytes of patients receiving L-asparaginase did not respond to phytohemagglutinin or specific antigens when cultured in media containing their own on-treatment serum, but responded at normal level when washed and cultured in media containing normal serum or their own pretreatment serum.

Phytohemagglutinin-induced blastogenic responses of lymphocytes from hematologically normal subjects were suppressed by the addition of serum from patients on L-asparaginase treatment.

¹ Supported by USPHS Contract PH 43 68 949, Collaborative Research Program, National Institute of Allergy and Infectious Diseases, NIH, and Grant CA 05831 from the National Cancer Institute, USPHS.

Received 10/22/69. Accepted 1/26/70.

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