CD28-Targeted Enzyme-Responsive Conformation-Switching Peptide Self-Assembly for Selective T-Cell Acute Lymphoblastic...

Area of Science:

• Oncology
• Nanomedicine
• Molecular Biology

Background:

• T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive cancer with few targeted treatments.
• CD28 is overexpressed on T-ALL cells, making it a potential therapeutic target.

Purpose of the Study:

• To develop an enzyme-responsive, self-assembling peptide (SA^p-CD28) targeting CD28 for T-ALL therapy.
• To investigate the mechanisms of SA^p-CD28-induced T-ALL cell death.

Main Methods:

• Development of SA^p-CD28, a peptide that self-assembles upon dephosphorylation.
• Transcriptomic and biochemical analyses to study CD28 downstream signaling.
• In vivo studies using Jurkat xenograft models.

Main Results:

• SA^p-CD28 self-assembles in the tumor microenvironment, forming nanooligomers that engage CD28.
• The peptide disrupts CD28 signaling, leading to oxidative stress, calcium overload, and cytoskeletal collapse.
• SA^p-CD28 showed significant antitumor activity, enhanced when combined with cytarabine.

Conclusions:

• SA^p-CD28 is a promising CD28-targeted nanotherapeutic for T-ALL.
• The strategy combines biochemical and mechanical mechanisms for selective cancer cell elimination.
• This approach may inspire treatments for other diseases.