Prophylactic Vaccination and Intratumoral Boost with HER2-Expressing Oncolytic Herpes Simplex Virus Induces Robust...

Area of Science:

• Oncology
• Virology
• Immunology

Background:

• Cancer vaccine development faces challenges like immune tolerance and limited clinical benefits.
• Oncolytic herpes simplex virus type 1 (oHSV-1) shows promise as cancer therapy but has limited efficacy in advanced cancers.
• Human epidermal growth factor receptor 2 (HER2) is overexpressed in many carcinomas.

Purpose of the Study:

• To construct and characterize a novel oHSV-1 virus (VG22401) expressing HER2.
• To evaluate the antitumor efficacy of VG22401 in a preclinical cancer model.
• To investigate the immunological responses induced by VG22401.

Main Methods:

• Constructed and characterized a novel oHSV-1 virus (VG22401) expressing HER2.
• Assessed viral replication and HER2 expression in cancer cells.
• Immunized mice with VG22401 and evaluated antibody binding, ADCC, CDC, and T cell responses.
• Tested antitumor efficacy in a bilateral syngeneic HER2(+) tumor model.

Main Results:

• VG22401 demonstrated efficient replication and HER2 expression in colorectal cancer cells.
• Immunization with VG22401 induced anti-HER2 antibodies, ADCC, and CDC.
• Peripheral priming with VG22401 followed by intratumoral boost enhanced antitumor efficacy and induced anti-HER2 T cell responses.
• VG22401 showed superior antitumor effects compared to a HER2-null backbone virus.

Conclusions:

• Peripheral priming with HER2-expressing oHSV-1 followed by an intratumoral boost is a promising cancer immunotherapy strategy.
• This approach significantly enhances antitumor immunity and efficacy.
• VG22401 represents a potential novel therapeutic agent for HER2-expressing carcinomas.