Cancer Vaccines: Bench to Bedside

Abstract

The immune system has immense potential in cancer therapy as it is individualized, precision driven and robust, however, it is associated with challenges of its own that include immune evasion, development of tolerance and a sustained tumor rejection response. Recent FDA approval of several checkpoint inhibitors, anti-CTLA4, anti-PD-1, has re-invigorated cancer immunology by demonstrating that tolerance to cancer can be broken to induce a sustained immune response in patients. Active immunization with multivalent tumor associated antigens (TAA), however, is still a challenge. We have developed two specific distinct methods to generate multivalent antigens capable of tumor regression in prostate cancer and melanoma. In prostate cancer, we have generated specific multivalent peptide mimetics using phage display synthetic peptide libraries capable of metastatic tumor regression in an animal model. In melanoma, we have used a vaccinia virus based antigen retrieval technology to generate a multivalent antigenic vaccine. The antigenic repertoire is well defined. A protocol for the melanoma vaccine is FDA approved for clinical Science, Vol. 2016, 33-60. doi: 10.13052/ijts2246-8765.2016.003 c 2016 34 N. Tuli et al. trials. We envision defining the humoral and cellular immune response to combine our active vaccine strategy with other treatment modalities including approved checkpoint inhibitors anti-CTLA4 and anti-PD-1. We believe our vaccine candidates are a new generation of immune-therapeutics that can prolong cancer free survival and prevent secondary recurrences. Our studies have challenged the existing paradigms to re-define cancer immunotherapy that bridges the gap between humoral and cellular immunity by combining active immune response with negative checkpoint inhibitors thus activating pre-existing dormant immune response. International Journal of Translational