technology

 

CVac™ therapy is a personalized immunocellular therapeutic that has been investigated for the treatment of epithelial cancer.

The CVac™ treatment stimulates the patient‘s own immune system to target and destroy tumors.The product is manufactured and customized for each patient individually. The patient‘s own immune precursor cells are isolated from their blood by a process called leukapheresis. These cells are matured in the laboratory and treated with a tumor-specific cell surface protein called mucin 1.

The unique form of mucin 1 is present in great amounts on epithelial tumors, thus it is a specific antigen and a favorable target for a cancer therapy.

ANTIGEN TARGET: MUCIN 1

Mucin 1 is a cell surface glycosylated phosphoprotein

Normal MUC1

Mucin

Tumor MUC1

  • More complex O-linked sugar chains
  • Glycosylated
  • Tandem repeat sequence (VNTR-variable number tandem repeat)
  • Simpler and fewer sugar chains
  • Underglycosylated
  • “Naked“ structure carbohydrate and peptide epitopes are exposed

The dendritic cells process the mucin 1 antigen and are then frozen for later shipment to the physician for administration to the patient.

At the clinic, CVac™ is thawed and injected intradermally (under the surface of the skin). The CVac™ then moves through the patient’s blood stream, and as CVac™ comes in contact with immune cells (T cells), it activates them to recognize and subsequently destroy tumour cells producing the tumor form of mucin 1 protein.

TREATMENT OVERVIEW:Treatment Overview

CVac™ has been investigated for epithelial ovarian cancer patients in remission, with Phase II results suggesting efficacy in second remission patients; results demonstrated extension of disease remission and overall survival benefit.

MODE OF ACTION:

Dendritic cells are a subset of white blood cells whose primary role is to educate the immune system to recognize foreign proteins; in the case of CVac™, the dendritic cells educate the immune system to detect and destroy a cancer protein. In the body, when the dendritic cell encounters foreign material it generates a recognition signal on its cell surface and when it comes into contact with T cells, triggers the T cells to respond and kill that foreign material. With CVac™, the manufacturing process exposes the dendritic cell to a unique cancer protein so that when CVac™ is administered back into the patient, the natural process for the dendritic cell to interact with, and stimulate T cells occurs.

Processing the dendritic cells outside of the patient’s own body may facilitate the cells to overcome the evasive mechanisms of the tumor by educating the body’s own immune system to fight the tumor.

The tumor antigen being targeted is a modified mucin 1. Mucin 1 is expressed by normal tissue in the body but has different (modified) characteristics on tumor cells so the immune response will be specific to the tumor tissue.

Interestingly, this is a molecule expressed by a variety of tumors including breast, ovarian, prostate, renal, pancreatic, lung, and colon cancers. CVac™ has been investigated to treat ovarian cancer patients, but there is an opportunity to evaluate CVac™ in other indications.

OPPORTUNITIES TO TARGET MUCIN 1:

Mucin 1 is overexpressed in a number of different adenocarcinomas:

Nasopharyngeal 100%
Lung (NSCLC) 99%
Breast 91%
Renal 84%
Ovarian 83%
SCC HN 82%
Colorectal 81%
Pancreatic 81%
Prostate 79%

Immunotherapy provides a unique therapy modality. By targeting a protein that exists only on tumor cells, it leaves normal tissues intact and has an excellent safety profile; side effects are minimal.

TREATMENT INDUCES CLINICALLY MEANINGFUL PROGRESSION-FREE SURVIVAL AND OVERALL SURVIVAL

Dosing of a 63 patient Phase II study was completed in 2013. Final PFS data was released in May 2014 while final OS data was released in May 2015.

TRIAL DESIGN:

  • Patients had stage III or IV ovarian cancer that were in first or second remission after surgery and/or chemotherapy and were entered into the study within 12 weeks after the last dose of chemotherapy that resulted in clinically complete remission
  • Patients were randomized to receive either observational standard of care (OSC) or therapy
  • Therapy was administered intradermally at six to eight injection sites and up to 10 administrations were given over 48 weeks
Progression Probability

TRIAL RESULTS:

  • In 20 second line remission (CR2) patients, there was a clinically significant improvement in PFS of at least 8 months when compared with the OSC group
  • Mature OS data for both groups showed that CR2 patients had a clinically meaningful 16+ month improvement in OS benefit with the median not yet being reached
  • Immune monitoring and safety data demonstrated that the therapy is well tolerated

Survival Probability