Alphavirus-Based Vaccines

Lundstrom, Kenneth

In another clinical trial, alphavirus particles expressing the carcinoembryonic antigen (CEA) were repeatedly administered to patients with metastatic cancer [98] . CEA-specific antibodies were able to mediate antibody-dependent cellular cytotoxicity against tumor cells from human colorectal cancer metastases. Furthermore, patients with CEA-specific antibodies encouragingly showed extended overall survival. Similarly, VEE replicons expressing the prostate-specific membrane antigen (PSMA) were applied for a human trial of patients with metastatic cancers at five doses of 0.9 × 10 7 IU or 3.6 × 10 7 IU [99] . At the lower dose, no PSMA-specific cellular response was obtained, but a weak PSMA-specific signal was detected by ELISA. Disappointingly, the higher dose showed no PMSA-specific response. The trial demonstrated that while there was neither clinical benefit nor robust immune responses, there were no toxicities associated with the immunization, and the VEE-PMSA particles were well tolerated. However, as neutralizing antibodies were elicited, the dosing might be suboptimal, requiring some further optimization.