Cancer-associated SCM-recognition, immunedefense suppression, and serine protease protection peptide. Part II. Immunedefense suppressive effects of the CRISPPs peptide.
The cancer SCM-recognition, immunedefense suppression, and serine protease protection (CRISPP) peptide, a product of a hereditary or acquired heritable alpha 1-PI gene DNA mutation in cancer cells, is a potent suppressor of the natural killer (NK) and lymphokine activated killer (LAK) cytotoxicity against cancer cells. The "NK suppression epitope" encompasses amino acid residues 8 to 29 of the 29 amino acid sequence of the CRISPPs peptide. The NK suppression is peptide dose and incubation time dependent. The formation of conjugates between effector and target cells is not affected by the peptide, but the release of interleukin-2 (IL-2) and of tumor necrosis factor-alpha (TNF alpha) from lymphocytes is significantly decreased after treatment of lymphocytes with the CRISPPs peptide. The suppression of NK and LAK activity of lymphocytes by the CRISPPs peptide cannot be removed by washing, nor can it be reversed by subsequent treatment with recombinant interleukin-2 (rIL-2). However, autologous cell-free blood plasma, especially plasma ultrafiltrates of molecular weights higher than 100 kDa, can restore up to 83% of the NK activity. Scavenging of the CRISPPs peptide with anti-CRISPPs antibodies prevents the suppression of NK cytotoxicity. The relevance of CRISPP peptides for adoptive immunotherapy is discussed.
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Beckman Instruments Inc., Diagnostic Systems Group, Brea, CA 92621.
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D003602:Cytotoxicity, Immunologic / Q000187:drug effects*; D004306:Dose-Response Relationship, Immunologic; D000939:Epitopes / Q000302:isolation & purification*; D006801:Humans; D007376:Interleukin-2 / Q000378:metabolism; D015979:Killer Cells, Lymphokine-Activated / Q000187:drug effects / Q000276:immunology*; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology*; D009363:Neoplasm Proteins / Q000494:pharmacology*; D013997:Time Factors; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects / Q000378:metabolism
D000939:Epitopes; D007376:Interleukin-2; D009363:Neoplasm Proteins; D014409:Tumor Necrosis Factor-alpha; C079042:cancer-recognition, immunedefense suppression, serine protease protection peptide