NOVEL-PEPTIDE-BASED ANTICANCER IMMUNOTHERAPEUTIC AGENT

Smart overview of the Invention

The disclosed invention introduces a novel peptide-based anticancer immunotherapeutic agent utilizing melittin and its variants or analogues. This agent specifically targets ITGB2, a protein expressed on the cell membrane of M2 tumor-associated macrophages (TAMs). By binding to ITGB2, the agent effectively kills these macrophages, which are known to promote tumor growth and metastasis. The invention also includes conjugates where a pro-apoptotic peptide or anticancer drug is linked to melittin, enhancing the apoptotic effects on M2 TAMs.

Background

Traditional cancer therapies often lead to significant side effects due to their non-selective nature, affecting both cancerous and normal cells. Immunotherapy has emerged as a promising alternative by leveraging the body's immune system to target cancer cells more selectively. However, existing immunotherapies often fall short in treating solid tumors due to the suppressive tumor microenvironment. M2-type TAMs within this microenvironment support tumor growth and metastasis, making them a critical target for new therapeutic strategies.

Technical Solution

The invention provides a pharmaceutical composition comprising a conjugate of melittin or its variants with a pro-apoptotic peptide or anticancer drug. This composition specifically removes tumor-associated macrophages from the tumor microenvironment. The method involves administering this conjugate to cancer patients, aiming to prevent or treat cancer by disrupting the supportive niche around tumor cells without directly attacking them.

Advantageous Effects

The targeted approach of this therapeutic agent allows for the specific binding and elimination of M2-type TAMs, thereby reducing their role in promoting tumor progression. The conjugation with pro-apoptotic peptides or anticancer drugs significantly enhances the apoptotic effect on these macrophages. As a result, this method effectively suppresses tumor growth and metastasis while minimizing the side effects associated with conventional therapies.

Supporting Data

• Figure 1: Demonstrates TAMpep's affinity for M2 macrophages using flow cytometry.
• Figures 2-4: Identify proteins binding to TAMpep in M2 macrophages through various analytical techniques.
• Figures 5-11: Confirm ITGB2 expression and interaction with TAMpep826 in M2 macrophages.
• Figures 12-25: Illustrate binding sites, binding affinities, and effects of TB511 in cancer models.