Abstract 5780
Background
Anti-PD-1 blocking monoclonal antibodies (mAbs) such as nivolumab or pembrolizumab have shown potent anti-tumor effects in different metastatic cancers. Similarly, anti-HER-2 mAbs such as Herceptin and Perjeta are approved for breast cancer. These mAbs are only effective in 10-25% of cancer patients, and are limited by high costs, side effects and development of resistance. Contrary to treatment with monoclonal antibodies, chimeric B-cell cancer vaccines incorporating a “promiscuous” T cell epitope have the advantage of safer and cheaper alternatives, producing a specific immune response that induces memory B & T cell responses, while reducing immune evasion, suppression and resistance.
Methods
We have translated two HER-2 combination peptide vaccines (B-Vaxx) to the clinic in a Phase 1/2b trial to safely deliver curative and transformative cancer immunotherapies to advanced cancer patients. We have created and established the development of a novel B-cell peptide vaccine (Key-Vaxx) with high immunogenicity that binds to human PD-1 and produces tumor inhibition in vivo in two animal models of colon cancer. We will describe the CT-26, CT26-HER2 and MC38 tumor models in Balb/c and C57/Bl6 used to test for synergistic effects of anti-PD1 immunization therapy in combination with anti-HER2 immunization therapy. The immunogenicity/optimal immunologic dose and toxicity profile was investigated in beagle dogs.
Results
We show robust HER-2 and PD-1 antibody responses in mice, beagle dogs and non-human primates. The individual (PD-1) or combined vaccination (B-Vaxx)) was effective in reducing tumor growth in a Balb/c and C57Bl/6 syngeneic model of colon carcinoma and exhibited superior activity compared to the positive gold control anti-mouse PD-1 (CD279) monoclonal antibody.
Conclusions
Development of PD-1 B-cell vaccine was successful, showing no evidence of toxicity or autoimmunity in mice, rabbits and beagle dogs. The combination vaccines could provide improved outcomes in early stage disease sparing patients the toxicity of chemotherapy. A phase 1 clinical trial with the PD-1 vaccine is under planning.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
NIH; Imugene.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
5383 - A pilot trial to investigate the impact of a personalised self-management lifestyle programme using mobile technology on the health and wellbeing of cancer survivors
Presenter: Mary Grace Kelly
Session: Poster Display session 3
Resources:
Abstract
5084 - The BRIGHTLIGHT national survey of the impact of specialist teenage and young adult cancer care on caregivers’ information and support needs
Presenter: Rachel Taylor
Session: Poster Display session 3
Resources:
Abstract
4328 - Life beyond cancer: Occupational health care service support in returning work experienced by cancer survivals
Presenter: Minna Nurmi
Session: Poster Display session 3
Resources:
Abstract
3337 - Investigating the factors related to primary caregivers' burden in oncology patients in Greece
Presenter: Ourania Govina
Session: Poster Display session 3
Resources:
Abstract
3387 - Factors Influencing the Level of Emotional Support from Nurses Perceived by Patients Undergoing Haematopoietic Stem Cell Transplantation in Protective Isolation
Presenter: Michela Piredda
Session: Poster Display session 3
Resources:
Abstract
935 - Progressive Muscle Relaxation and Guided Imagery Techniques and the Way of Coping of Parents of Children with Malignancies: A randomized controlled trial
Presenter: Tsitsi Theologia
Session: Poster Display session 3
Resources:
Abstract
3457 - Pharmacist and Nurse Led Melanoma Immunotherapy Clinic
Presenter: Dharmisha Chauhan
Session: Poster Display session 3
Resources:
Abstract
5160 - Measuring the impact of the Irish Cancer Society's Cancer Information Services
Presenter: Aileen McHale
Session: Poster Display session 3
Resources:
Abstract
4297 - It's Great to Talk
Presenter: Noreen Andersen
Session: Poster Display session 3
Resources:
Abstract
4444 - Impact of Burn-Out Syndrome in Oncology personnel and its improvement through specific interventions
Presenter: Inmaculada Ortega
Session: Poster Display session 3
Resources:
Abstract