Recombinant polyclonal antibodies for cancer therapy

Area of Science:

• Immunology
• Oncology
• Biotechnology

Background:

• Monoclonal antibodies (mAbs) are used in cancer therapy, but temporary remissions occur due to tumor cell escape variants.
• Tumor cell escape variants emerge, rendering mAbs ineffective and limiting therapeutic success.
• Multi-targeting with polyclonal antibodies could overcome resistance and enhance effector functions for tumor cell destruction.

Purpose of the Study:

• To develop a technology for generating recombinant polyclonal antibody libraries (PCALs) for cancer therapy.
• To minimize the emergence of tumor cell escape variants observed with current monoclonal antibody treatments.
• To create a versatile platform for producing polyclonal antibodies with enhanced anti-cancer activity.

Main Methods:

• Construction and selection of tumor-reactive Fab phage display libraries.
• Mass conversion of selected Fabs into full-length polyclonal antibody libraries (PCALs) of any isotype and species.
• Generation of prototypic PCALs against human colorectal cancer cell lines.

Main Results:

• Demonstrated the ability to obtain diverse recombinant antibody libraries enriched for reactivity to cancer cells over normal cells.
• Successfully generated prototypic PCALs against human colorectal cancer.
• Established a foundation for producing PCALs with improved cancer-specific targeting.

Conclusions:

• Recombinant polyclonal antibodies (PCALs) represent a viable strategy to overcome tumor escape mechanisms in cancer therapy.
• The developed technology enables the generation of PCALs with enhanced cancer-to-normal cell reactivity ratios.
• Future success hinges on generating, characterizing, and mass-producing PCALs with broad reactivity for diverse cancer types.