Back to resources

Molecular imaging of cancer vaccines

Maarten Brom, PhD

Vaccines are successfully used to prevent and treat infectious diseases. These vaccines use weakened or antigens of viruses or bacteria to activate the immune system, to destroy the pathogen. The last decades researchers developed vaccines to prevent or treat cancer. The principle of cancer vaccines is identical: the use of tumor specific or associated antigens to stimulate the immune system to destroy the tumor cells. However, development of cancer vaccines is way more challenging. Molecular imaging can play an important role in making this process more efficient for you.

What are cancer vaccines and why are they hard to develop?

The principle of all cancer vaccines is identical: you activate the immune system by presenting it with a protein that is highly expressed on the cancer cells. The immune system will then generate an immune response against these proteins and destroy the tumor cells.

For cancer vaccines a strong cellular response is needed to destroy tumor cells. This is of less importance for infectious diseases, where a humoral response (antibody production) is usually enough to eliminate the pathogen.

With cancer vaccines, you target cells and usually antigens that are derived from your own body. Opposite to infectious diseases, where you target a foreign pathogen that enters your body. This makes it more difficult to select a target for cancer vaccines.

Another obstacle for developing cancer vaccines is that they tend to induce a milder immune reaction. This makes it harder to develop a strong enough immune reaction to kill cancer cells. Finally, the local effect of the vaccines on the tumor is difficult to measure. You can measure the systemic immune response, but this might not reflect the immune response in the tumor.

Four types of cancer vaccines.

In principle, there are four types of cancer vaccines:

Cell based cancer vaccines

Cell based vaccines consist of whole cells or cell fragments that express the target. The most promising cell-based vaccines are dendritic cells. These immune cells can be stimulated ex vivo to express the target of interest. Once you administer these stimulated dendritic cells into a cancer patient, the dendritic cells present the antigen to the immune system. As a result, the immune system develops an immune response against the tumor.

Virus-based cancer vaccines

You can introduce the genetic sequence for the tumor associated target/protein of interest in the genome of the virus. These types of vaccines are called virus-based cancer vaccines. When you administer the virus to patients, the virus will infect the patients’ cells to produce the tumor associated protein. This way, you stimulate the immune system to induce an immune response against the tumor.

Peptide-based cancer vaccines

Peptide-based cancer vaccines work as follows. You select a part of the sequence of the amino acid sequence of the tumor associated antigen. Next, you synthesize this particular amino acid sequence (a peptide). When you administer the peptide to the cancer patients, the immune system will induce an immune response against the peptide, and thus, the tumor associated antigen.

DNA or RNA cancer vaccines

Similar to viral vaccines, you can introduce the sequence of a tumor associated antigen in the DNA or RNA sequence of the vaccine. After you administer the vaccine to the cancer patient, the genetic material is transfected in cells of the body and start to produce the tumor antigen. This results in a tumor specific immune response.

Illustrating the four main types of cancer vaccines

Molecular imaging of cancer vaccines.

When you administer a cancer vaccine to a patient, you want to follow the therapeutic efficacy during the therapy. You can measure the immune response in the blood of the patient. Another way is to measure the tumor volume by CT or MRI to determine the effect of the therapy on tumor growth. However, you can’t always predict efficacy on these outcome measures.

To determine efficacy, you have to wait for a long time to see the overall survival of the patients treated with a cancer vaccine. Especially when you compare it with conventional therapy. Ideally, during clinical trials you want to have an interim measure of the efficacy of the cancer vaccine. You can use molecular imaging as an interim measure.

Direct imaging of cancer vaccines.

You can directly label your cancer vaccines to track it after administration. A successful example is the labeling and imaging of dendritic cells. You can label dendritic cells with MRI contrast agents or radionuclides for PET and SPECT. For MRI, you can prelabel your dendritic cells with fluorine-19 nanoparticles before administration into patients. After administration, you can track the dendritic cells over time.

Alternatively, you can label the dendritic cells with indium-111 or zirconium-89 for SPECT or PET imaging, respectively. Effective (cellular) cancer vaccines will home to the lymph nodes and spleen where they can present the tumor associated antigens to immune cells.

Imaging in the downstream effects of cancer vaccines.

With direct imaging of cancer vaccines, you can visualize where the vaccine interacts with the immune system. It doesn’t give you information on the effect of the vaccines on anti-tumor effects. A successful cancer vaccine should induce a strong infiltration of immune cells in the tumor. You can visualize immune cell influx with PET imaging using a radiolabeled tracer that specifically targets these infiltrating immune cells.

For example, you can visualize CD8-positive T-cells with a zirconium-89-labeled antibody for PET. For a successful cancer vaccine, you expect a high number of infiltrating CD8+ T-cells in the tumor (and in the lymph nodes and spleen where the T-cells are activated) and no infiltration in healthy tissue.

You can also use a radiolabeled tracer to target the cancer associated antigen of interest. Before vaccine therapy, you measure the expression of the antigen. After vaccine administration, you expect a decrease in signal when the therapy is effective. You can also use this technique to evaluate antigen expression in healthy tissue to predict side effects.

With molecular imaging you can monitor the efficacy of cancer vaccines in first-in-human trials. At TRACER, we can assist you to select the optimal imaging strategy for your cancer vaccines. With that molecular imaging strategy, you can determine the efficacy of your vaccine at an earlier stage as compared to the classical long term outcome measure of tumor shrinkage and survival.

References.

  1. Lopes, Alessandra & Vandermeulen, Gaëlle & Preat, Veronique. (2019). Cancer DNA vaccines: current preclinical and clinical developments and future perspectives. Journal of Experimental & Clinical Cancer Research. 38. 10.1186/s13046-019-1154-7.

Other blogs

| See all blogs
Blog

Why and how to standardize quantified PET scans in your trial

Milou Noltes, MD, PhD
Blog

How your Phase 2 or 3 trial can benefit from molecular imaging

Maarten Brom, PhD
Blog

An introduction to optoacoustic imaging in drug development

Milou Noltes, MD, PhD