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
3839 - Fenofibrate impairs pro-tumorigenic potential of cancer stem cell-like cells within drug-resistant prostate cancer cell populations.
Presenter: Tomasz Wróbel
Session: Poster Display session 3
Resources:
Abstract
3842 - Effect of docetaxel-resistance on the reactivity of prostate cancer cells to metformin
Presenter: Jessica Catapano
Session: Poster Display session 3
Resources:
Abstract
5198 - Cell plasticity and taxanes resistance in metastatic prostate cancer: ESRP1 as a predictive biomarker of taxane response
Presenter: Natalia Jimenez
Session: Poster Display session 3
Resources:
Abstract
2981 - Effect of Selumetinib plus AZD8186 treatment on Cabazitaxel sensitivity in docetaxel-acquired resistant metastatic prostate cancer cell lines
Presenter: Vicenc Ruiz de Porras
Session: Poster Display session 3
Resources:
Abstract
2779 - Anti-tumor activity of cediranib, a pan-inhibitor of vascular endothelial growth factor receptors, in pancreatic ductal adenocarcinoma cells
Presenter: Majid Momeny
Session: Poster Display session 3
Resources:
Abstract
1782 - The molecular mechanisms of EpCAM in regulating tumor progression and development of anti-EpCAM antibodies for colon cancer diagnosis and therapy
Presenter: Han-chung Wu
Session: Poster Display session 3
Resources:
Abstract
1322 - Detection of microRNAs as biomarker for anti-EGFR antibody resistance in colon cancer patients
Presenter: Jens Hahne
Session: Poster Display session 3
Resources:
Abstract
1579 - Serum exosomal microRNA-199b-5p as a novel circulating biomarker to predict response of preoperative chemoradiotherapy for locally advanced rectal cancer
Presenter: Dong Won Baek
Session: Poster Display session 3
Resources:
Abstract
1761 - Live biobank of patient-derived organoids from Thai colorectal cancer patients enables clinical outcome prediction
Presenter: Pariyada Tanjak
Session: Poster Display session 3
Resources:
Abstract
3542 - The biological implications of PDCD6 dysregulation in colorectal cancer
Presenter: Romina Briffa
Session: Poster Display session 3
Resources:
Abstract