The multicompartmental p32/gClqR as a new target for antibody-based tumor targeting strategies
David Sánchez-Martín1, Angel M Cuesta, Valentina Fogal
1Molecular Immunology Unit, Hospital Universitario Puerta de Hierro Majadahonda, 28222 Madrid, Spain.
Abstract:
Tumor-associated cell surface antigens and tumor-associated vascular markers have been used as a target for cancer intervention strategies. However, both types of targets have limitations due to accessibility, low and/or heterogeneous expression, and presence of tumor-associated serum antigen. It has been previously reported that a mitochondrial/cell surface protein, p32/gC1qR, is the receptor for a tumor-homing peptide, LyP-1, which specifically recognizes an epitope in tumor cells, tumor lymphatics, and tumor-associated macrophages/myeloid cells. Using antibody phage technology, we have generated an anti-p32 human monoclonal antibody (2.15). The 2.15 antibody, expressed in single-chain fragment variable and in trimerbody format, was then characterized in vivo using mice grafted subcutaneously with MDA-MB-231 human breast cancers cells, revealing a highly selective tumor uptake. The intratumoral distribution of the antibody was consistent with the expression pattern of p32 in the surface of some clusters of cells. These results demonstrate the potential of p32 for antibody-based tumor targeting strategies and the utility of the 2.15 antibody as targeting moiety for the selective delivery of imaging and therapeutic agents to tumors.
Insights
Researchers developed a new antibody targeting the p32 protein, which is found on tumor cells. This antibody shows selective tumor uptake in preclinical models, highlighting p32 as a promising target for cancer therapies.
Area of Science:
- Oncology
- Immunology
- Molecular Biology
Background:
- Traditional cancer targets like cell surface antigens and vascular markers have limitations including accessibility and heterogeneous expression.
- The protein p32/gC1qR, located on mitochondria and the cell surface, serves as a receptor for the tumor-homing peptide LyP-1.
- p32 is recognized by LyP-1 on tumor cells, tumor lymphatics, and tumor-associated macrophages, indicating its potential as a specific tumor target.
Purpose of the Study:
- To generate a novel human monoclonal antibody targeting the p32 protein.
- To evaluate the in vivo tumor-targeting capabilities of the anti-p32 antibody.
- To assess the potential of p32 as a target for antibody-based cancer intervention strategies.
Main Methods:
- Utilized antibody phage technology to generate a human monoclonal antibody against p32, designated 2.15.
- Expressed the 2.15 antibody in single-chain fragment variable (scFv) and trimerbody formats.
- Characterized antibody tumor uptake and distribution in mice bearing subcutaneous MDA-MB-231 human breast cancer xenografts.
Main Results:
- The 2.15 antibody demonstrated highly selective uptake in tumors.
- Intratumoral distribution of the antibody correlated with the surface expression of p32 on cell clusters within the tumor.
- The antibody's targeting was consistent across different formats (scFv and trimerbody).
Conclusions:
- The p32 protein is a viable target for antibody-based tumor-targeting strategies.
- The 2.15 anti-p32 antibody is a valuable targeting moiety for selective delivery of agents to tumors.
- This antibody holds potential for developing targeted imaging and therapeutic applications in cancer treatment.
