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
4868 - Evaluation of markers associated with efficacy of abiraterone acetate plus prednisone (AAP) in patients (pts) with castration-sensitive prostate cancer (mCSPC) from the LATITUDE study
Presenter: Kim Chi
Session: Poster Display session 3
Resources:
Abstract
4837 - LRP2, a potential new biomarker for Chinese younger aged intrahepatic cholangiocarcinoma patients
Presenter: Xiaoliang Shi
Session: Poster Display session 3
Resources:
Abstract
1286 - Reanalysis of the efficacy of molecular targeted agents (MTAs) given in the randomized trial SHIVA01 according to the ESMO ESCAT scale of actionability
Presenter: Aurelie Moreira
Session: Poster Display session 3
Resources:
Abstract
2736 - Comparison of Platforms for Determining Tumor Mutational Burden (TMB) From Blood Samples in Patients With Non-Small Cell Lung Cancer (NSCLC)
Presenter: Jonathan Baden
Session: Poster Display session 3
Resources:
Abstract
5045 - Comprehensive Pan-Cancer analysis of somatic mutations in drug transporters to reveal acquired and intrinsic drug resistance in 3149 metastatic cancer patients
Presenter: Sander Bins
Session: Poster Display session 3
Resources:
Abstract
4577 - Pan-Cancer Genomic Landscape of the Cyclin D1/FGF3,4,19 (11q13) Amplicon Including Associations with HPV Status, and ESR1 and AR Alterations
Presenter: Jennifer Johnson
Session: Poster Display session 3
Resources:
Abstract
5366 - Co-occurrence of NTRK fusions with other genomic biomarkers in cancer patients
Presenter: Xiaolong Jiao
Session: Poster Display session 3
Resources:
Abstract
4084 - Prospective comparative study of next-generation sequencing on fine needle aspirations versus core needle biopsies in cancer patients included in SHIVA02 trial
Presenter: Julien Masliah-Planchon
Session: Poster Display session 3
Resources:
Abstract
6017 - First national External Quality Assessement for the interpretation of somatic variants: assessment of 25 variants in colorectal, lung, ovarian cancers and melanoma in France
Presenter: Etienne Rouleau
Session: Poster Display session 3
Resources:
Abstract
2283 - Prospective testing of circulating tumor DNA in metastatic breast cancer facilitates clinical trial enrollment and precision oncology
Presenter: Andjelija Bujak
Session: Poster Display session 3
Resources:
Abstract