Identification and immunotherapeutic targeting of antigens induced by chemotherapy

Area of Science:

• Oncology
• Immunotherapy
• Cancer Biology

Background:

• Cancer cells exhibit distinct responses to chemotherapy compared to normal cells.
• Chemotherapy can induce the expression of specific cell-surface proteins on tumor cells.

Purpose of the Study:

• To exploit the differential response of cancer cells to chemotherapy.
• To identify and target tumor-specific cell-surface proteins induced by chemotherapy.

Main Methods:

• Utilized irinotecan (CPT-11) to induce expression of tumor-specific antigens.
• Developed a cytotoxin-armed antibody targeting the LY6D/E48 antigen.
• Administered combination therapy (antibody + CPT-11) to colorectal tumor xenografts in mice.

Main Results:

• A cytotoxin-armed antibody targeting the LY6D/E48 antigen, induced by CPT-11, achieved complete regression of colorectal tumors.
• Combination therapy with CPT-11 and the antibody was significantly more effective than either agent alone.
• This approach suggests a potential for enhanced therapeutic index in drug combinations.

Conclusions:

• Targeting chemotherapy-induced antigens offers a novel strategy for cancer therapy.
• Immunotherapy combined with chemotherapy can overcome limitations of individual treatments.
• This approach may improve treatment efficacy for various cancers by targeting drug-induced antigens.