Dr. Saskia Biskup

Latest Updated on August 30th, 2021

 

I have arrived to the doctor’s office on time, and it was my first time to Germany.   It was a beautiful city and powerful country.      
 

The Report 

The below is the outcome of the first visit to doctor’s office (and Germany), as received from the doctor  
 
We have met four times to induce the immune response. As you know, the aim of the treatment with the personalized vaccine in Germany is to activate the patient’s own immune system to recognize and destroy tumor cells. The mechanism takes advantage of the fact that the tumor cells are distinct from normal cells and can be recognized by specialized immune cells if those are trained against the tumor cells. Tumor mutations are highly patient- and tumor-specific and some of those lead to production of novel protein sequences. The tumor cells present some of those mutation-derived novel protein sequences (neoantigens) on their surface. These neoantigens are different from those in normal cells and tumor-specific T cells can be able to recognize them.
 
To use this knowledge for vaccine development we first identified the tumor-specific mutations. To identify such mutations, we performed exome analyses of DNA from both tumor (malignant tissue) and from the blood (as normal control) using next-generation sequencing
 
The analyses included:
  • Whole-exome sequencing of tumor and normal tissue
  • Whole tumor transcriptome
  • Identification of tumor-specific nonsynonymous mutations (mutations that may lead to altered protein sequences)
  • Compilation of a clinical report including treatment recommendations
  • Genotyping of the patient’s HLA molecules
  • Prediction of which tumor-specific mutated peptides are most probably presented on the tumor cell surface by the patient-specific HLA types using novel computational methods
  • Database analysis to investigate the expression of the respective genes in this tumor type
  • Analysis of which peptides can be synthesized and dissolved in an injectable solution
  • Selection and recommendation of peptides which are predicted to elicit the most powerful immune response against the tumor: compilation of report.

Based on these analyses, to manufacture the personalized tumor neoantigen-specific peptide vaccine, the following steps have been performed:

  • Synthesis of the desired number of peptides
  • Preparation and quality control of the injectable multi-peptide vaccines (sufficient doses for one year)

 The personalized vaccine is applied along with an adjuvant (typically GM-CSF, Leukine® or Aldara®) to increase the stimulation of the immune system.

 

Repeated vaccinations are now being performed regularly according to a fixed treatment plan. The plan includes

  • A priming phase (4 vaccinations within 10 to 12 days) and
  • Subsequent monthly injections for about 10 months.
 

 

First vaccination: 23.08.2021

Application of the personalized vaccine together with Aldara® and Leukine® and blood draw for immune monitoring

 

Second vaccination: 24.08.2021

Application of the personalized vaccine together with Aldara® and Leukine® 

 

Third vaccination: 25.08.2021

Application of the personalized vaccine together with Aldara® and Leukine®

 

Fourth vaccination: 26.08.2021

Application of the personalized vaccine together with Aldara® and Leukine®

 

After these priming injections, we recommend administering boosting vaccinations every 4 to 6 weeks.  To the best of our knowledge and according to our experience, the treatment is in general well-tolerated.  We were happy to see that you tolerated the first four vaccinations very well.

 

Monitoring the immune response to the treatment is important for gauging its success and can help prevent potentially more severe side effects. As such immune monitoring is strongly recommended as an important
monitoring mechanism along with the vaccine treatment. We recommend doing the monitoring when Mohammed Banat will be here for the seventh vaccination.

 

For immune monitoring, blood is collected during the first injections and every 3 to 4 months thereafter. Immune cells (T cells and antigen presenting cells) are isolated and incubated with peptides of the vaccination cocktail. T cells specifically activated by a peptide will be identified by intracellular cytokine staining and FACS analysis. The patient receives a report highlighting the vaccine peptides that induced a significant immune (T cell) response. This information can in turn be used to control the immunogenicity of the vaccination regime and to further adjust the treatment plan.

 

From a clinical perspective immune monitoring is the only way to monitor the immune system. It is also the only way to quantitatively gauge the efficacy of the vaccine therapy. This information is also critical for effectively timing and spacing the vaccine injections for maximum impact.