A new immunomodulatory vaccine approach is being developed in which immunization with a carbohydrate mimetic peptide P10s (CMP) (also called a mimotope) is used to elicit carbohydrate reactive antibodies. CMP induced antibodies have different functionalities. Some may have cytotoxic characteristics to tumor cells, some may mediate NK cells for attacking tumor cells and some may remodel the glycan surface on tumor cells. The P10s CMP can induce immune responses in humans in which the antibodies are cytotoxic to tumor cells, activates p46 expressing Natural Killer cells and human antibodies reactive with the carbohydrate mimetic peptide can block migration of tumor cells and that human antibodies reactive with the carbohydrate mimetic peptide displays a degree of catalytic activity with amylase-like activity.
The novelty in the proposed vaccine mechanisms lies in: 1) showing that the CMP P10s induces humoral immune responses in cancer patients; 2) that NK cells are activated in vivo by the immunization strategy, 3) that the induced antibodies are cytotoxic; 4) the selection/induction of antibodies with catalytic activity (Abzyme) of preimmune/elicited anti-carbohydrate antibodies through polyspecific carbohydrate mimotope, and 5) the immunomodulatory application of such antibodies to kill tumor cells directly, activate NK cells and remodeling the carbohydrate antigen patterns on target cells.
A Phase I clinical trial was completed which demonstrated the safety and tolerability of the vaccine using a small group of participants who received five injections of the vaccine during a 23-week span. The vaccine, which is a first of its type tested in humans, was shown to induce antibody responses in the subjects. A Phase I/II clinical trial is underway in ER-positive breast cancer patients to evaluate the feasibility and efficacy of combining CMP P10s vaccination with neoadjuvant chemotherapy.