Exploiting Radiation Induction of Antigens in Cancer: Targeted Drug Delivery.

Area of Science:

• Oncology
• Immunology
• Radiotherapy

Background:

• Therapeutic antibodies are effective in advanced-stage cancer, with T-lymphocyte activators and antibody-drug conjugates showing promise.
• Radiation-inducible antigens are stress-regulated proteins over-expressed in cancer cells but not normal tissues.

Purpose of the Study:

• To review the use of radiation-inducible antigens for targeted cancer therapy.
• To discuss how radiotherapy can control the binding of therapeutic antibodies and antibody-drug conjugates to cancer cells.

Main Methods:

• Review of literature on therapeutic antibodies, radiation-inducible antigens, and their combination with radiotherapy.
• Focus on stress-regulated proteins like GRP78 and TIP1 as targets.

Main Results:

• Radiation-inducible antigens become accessible for antibody binding during cellular response to genotoxic stress.
• Antibodies targeting GRP78 and TIP1 enhance radiotherapy efficacy in preclinical models.
• Antibody-drug conjugates further improve cancer response when targeting these antigens.

Conclusions:

• Therapeutic antibodies targeting radiation-inducible antigens offer a strategy for advanced cancers.
• Radiotherapy can be used to control the specific binding of these antibodies and antibody-drug conjugates to tumors.