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Cancer-associated SCM-recognition, immunedefense suppression, and serine protease protection peptide. Part II.
Abstract:
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.
Insights
Cancer cells produce a CRISPP peptide that suppresses natural killer (NK) and lymphokine-activated killer (LAK) cell activity. Plasma or antibodies can restore NK cell function, suggesting therapeutic potential.
Area of Science:
- Immunology
- Molecular Biology
- Cancer Research
Background:
- The cancer SCM-recognition, immunedefense suppression, and serine protease protection (CRISPP) peptide is implicated in cancer immune evasion.
- This peptide is a product of alpha 1-PI gene mutations in cancer cells.
- CRISPP peptide suppresses natural killer (NK) and lymphokine-activated killer (LAK) cell cytotoxicity.
Purpose of the Study:
- To investigate the mechanism by which CRISPP peptide suppresses NK and LAK cell activity.
- To explore potential strategies for overcoming CRISPP-mediated immune suppression.
Main Methods:
- Assessing NK and LAK cell cytotoxicity against cancer cells.
- Analyzing the effect of CRISPP peptide on effector-target cell conjugate formation.
- Measuring cytokine release (IL-2, TNF-alpha) from lymphocytes after peptide treatment.
- Investigating the reversibility of suppression using washing, rIL-2, plasma, and antibodies.
Main Results:
- CRISPP peptide dose- and time-dependently suppresses NK and LAK cytotoxicity.
- Peptide does not affect effector-target cell conjugate formation but decreases IL-2 and TNF-alpha release.
- Suppression is irreversible by washing or rIL-2 treatment.
- Autologous plasma (especially >100 kDa ultrafiltrates) restores up to 83% of NK activity.
- Anti-CRISPPs antibodies prevent NK cytotoxicity suppression.
Conclusions:
- CRISPP peptide is a potent suppressor of cellular cytotoxicity against cancer cells.
- Plasma components and specific antibodies can counteract CRISPP-mediated immune suppression.
- These findings highlight the potential of CRISPP peptides and their modulators in adoptive immunotherapy.