Development and Characterization of a Novel Non-Lytic Cancer Immunotherapy Using a Recombinant Arenavirus Vector...

Area of Science:

• Oncology
• Immunology
• Virology

Background:

• Engineered viral vectors, particularly arenaviruses, are explored for cancer immunotherapy due to their ability to induce strong T cell responses.
• Arenaviruses are effective in eliciting potent and protective T cell immunity.

Purpose of the Study:

• To evaluate a novel, intravenously administered, replication-competent, non-lytic arenavirus-based vector technology for inducing antigen-specific anti-cancer T cell responses.
• To assess the safety and efficacy of arenavirus vectors HB-201 and HB-202 in patients with recurrent or metastatic HPV16+ cancers.

Main Methods:

• Preclinical studies in mice and human cells demonstrated arenavirus vector preferential infection of antigen-presenting cells and subsequent induction of CD8+ T cell responses.
• A Phase 1/2 clinical trial (NCT02110731) is evaluating HB-201 (LCMV-based) and HB-202 (Pichinde virus-based) vectors encoding HPV16 antigens E6/E7 in patients with HPV16+ cancers.
• Intravenous administration with optional initial intratumoral dose, with dose escalation/expansion.

Main Results:

• Arenavirus vectors preferentially infect antigen-presenting cells, leading to robust antigen-specific CD8+ T cell responses.
• Preclinical models showed T cell migration and infiltration into the tumor microenvironment, with evidence of immunological memory.
• Preliminary clinical data show HB-201/HB-202 monotherapy is immunogenic, increasing cytokines and expanding antigen-specific CD8+ T cells.
• Alternating HB-201/HB-202 injections led to up to 40% HPV16 E7/E6-specific CD8+ T cells in peripheral blood.
• Intravenous administration resulted in a 73% disease control rate in evaluable head and neck cancer patients.

Conclusions:

• Arenavirus vector-based immunotherapy is a promising strategy for generating antigen-specific anti-cancer T cell responses.
• The technology demonstrates safety and immunogenicity in a Phase 1/2 clinical trial for HPV16+ cancers.
• Intravenous administration of arenavirus vectors, particularly in combination, shows potential for significant anti-tumor activity.