The recurrence of cancer is one of the biggest challenges to successful treatment. With new vaccine nanodisks, it may be possible to combat this. Image credit: Flickr Commons
There are a few things that undermine any successful medical interventions against cancer, especially incomplete remission and subsequent recurrence. Recurrence is known for being unpredictable, and is often devastating to patients. Researchers are making headway against recurrence using a new approach: immunotherapeutic vaccine nanodiscs.1 Unlike many vaccines, the nanodisc vaccine is both therapeutic and prophylactic, allowing for the immune system to accelerate the killing of tumor cells while laying the basis for a quick reaction to later episodes of recurrence. In an additional departure from traditional vaccines, the nanodisc vaccine contains recipient-specific tumor neoantigen variants.
These tumor neoantigens are incorrectly expressed cellular proteins, and manifest only on tumor cells. Each vaccine recipient will have a different profile of neoantigens on their tumors, making targeting them with a nonspecific therapy an impossible task.2 In order to develop a nanodisc containing examples of the intended recipient’s tumor neoantigens, the tumor must first be biopsied. Once a sample is obtained, the tumor cells then undergo exome sequencing, allowing researchers to identify neoantigens based off of areas where the tumor’s DNA doesn’t form consensus strands with DNA from a non cancerous cell. After finding the neoantigens, all that remains is to generate neoantigen peptides and combine them with adjuvants and the carrier nanodisc.
All of this requires not only large amounts of data aggregation and management, but also intense interdepartmental collaboration that would further complicate this already complex task. In order to keep things moving and preserve valuable time and resources, researchers will want to utilize the most innovative software system available.
Using an Immunotherapeutic Nanodisc
Each batch of nanodiscs must be designed to the specification of its payload, since the physical interactions between the payload and the bilayer will differ. The nanodisc must also be able to permeate the recipient’s cell membranes and operate in the environment of the draining lymph node in order for the vaccine to be effective. Making a nanodisc delivery system isn’t easy, and assembly techniques have changed a lot since early development.3 Nanodiscs intended to be used as vaccines have to carry a substantial payload, carrying the neoantigens as well as immunostimulatory molecules.
There’s quite a few moving parts that have to come together within the immunotherapeutic system outlined by the new research:
- Identifying the tumor(s) to be targeted immunotherapeutically
- Sampling normal cells and tumor cells of the host
- Cosequencing the normal cells and tumor cells
- Identifying neoantigens by finding conflict between the healthy host cell sequence and the tumor cell sequence
- Generating variations of the neoantigen sequences
- Generating small quantities of peptides based off of the original and the variant neoantigen sequences
- Designing a nanodisc which can carry the neoantigen peptides and adjuvants
- Generating the designed nanodiscs and assaying their integrity
- Taking baseline measurements of the host’s systemic immune activation
- Deployment of vaccine-loaded nanodisc to the host
- Monitoring host for tumor remission
- After therapy, challenging the host with tumor neoantigens at different timepoints to assay the durability of vaccination effectiveness
The patient-specific nature of using the new vaccine design leads to a daunting amount of planning, data tracking, and data manipulation. Each step in vaccine development and subsequent treatment requires a complete understanding of the previous step’s data before proceeding. This data load will become even larger if a hypothetical nanodisc based vaccine proceeds into clinical trials.
Immunotherapy Meets Individuals
The improvement of nanodisc technology is exciting because it is likely to be used for vaccines and other therapeutics moving forward as well as cancer treatment. In the context of immunotherapy, nanodiscs are especially promising because of their ability to localize to immune system centers such as the lymph nodes. Because of this, understanding the data inputs required for nanodisc based immunotherapy is especially important. There are a number of unique datasets which must be tracked and manipulated effectively in order to perform research or development into immunotherapy applications of nanodiscs. From recipient disease information and immune profiles to tumor cell genomes and recipient-specific nanodisc templates, there is a whole range of interlocked information that must be sorted, analyzed and utilized.
The information contained in many of these data sets grows more complex as the therapy regime continues forward in time, with researchers eager to chew through the data in order to learn as much as possible. In addition to the added complexity, new insights can be derived by comparison of old data with new findings throughout the course of therapy. These kind of comparisons get to be quite numerous:
- Re-sequencing of tumor DNA after first round of treatment in order to see if a second round of treatment will need to alter the formulation of the nanodisc vaccine in light of new neoantigens
- Comparing the frequency of cytotoxic lymphocyte proliferation markers before and after treatment as a measure of general efficacy
- Comparing the frequency of neoantigen specific cytotoxic lymphocytes before antigen challenge but after initial vaccination to determine baseline efficacy
- Comparing neoantigen libraries encapsulated in the nanodisc with peptides presented by harvested mature dendritic cells from the lymph nodes to determine if immune activation is specific to the tumor neoantigens or merely a result of the adjuvants
- Comparing pre-treatment nonspecific tumor lysis markers during tumor recurrence with specific tumor lysis markers during remission to build profiles of disease phase transition
Given the massive informatics load that creating and utilizing nanodisc vaccines will entail, a superlative software package is required. Immunotherapy with nanodisc vaccines requires modeling, collaboration, experiment tracking, group analysis and data management above and beyond that which is needed for traditional vaccine development.
Designed to Cure is the experiment planning, tracking, management, modeling, and collaboration system that can handle the extremely demanding prospect of immunotherapeutic vaccine development. Using Designed to Cure, handling dozens of parallel data streams is possible. Contact us today to find out how we can help you get the most out of the latest research in immuno-oncology.
- “Designer vaccine nanodiscs for personalized cancer immunotherapy.” September 2016, http://www.nature.com/nmat/journal/vaop/ncurrent/full/nmat4822.html ↩
- “Tumor neoantigens: building a framework for personalized cancer immunotherapy.” September 2015, https://www.ncbi.nlm.nih.gov/pubmed/26258412 ↩
- “Self-assembly of single integral membrane proteins into soluble nanoscale phospholipid bilayers.” November 2003, http://onlinelibrary.wiley.com/doi/10.1110/ps.03267503/full#references ↩