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Information in PBMC Useful for Cancer Vaccine Design

Nov 12, 2014 1:00:58 PM / by Daisy

We could be headed towards developing cancer vaccines using genomic and proteomic information from PBMC.

When cancer cells undergo uncontrolled proliferation, they accumulate mutations (mistakes) in their DNA. But in a "chicken and egg" scenario, mutations in turn result in uncontrolled proliferating cancer cells. In either case, the resulting production of mutated proteins that were not present in the fetus, when the immune system developed, could potentially be seen as non-self (foreign) by the immune system in the adult.

Recent technological advances in DNA sequencing methods have made it possible to identify neoepitopes (new proteins that arise due to DNA mutations and which are detected by the immune system). We recently highlighted how peripheral blood mononuclear cell (PBMC) samples can be used to gather DNA data in specific diseases from the patient population. Researchers are also able to obtain bioinformation on neoepitopes in cancer using PBMC from patients.

PBMC Do uncontrolled cell proliferations cause mutations, or do mutations cause uncontrolled cell proliferations? Whatever the case, genomic information residing in PBMC could aid in vaccine development. Image credits: http://commons.wikimedia.org/

While hundreds of neoepitopes can be identified using PBMC samples from cancer patients, the challenge lies in pinpointing those that can be used for therapeutic benefit. Once scientists learn how to locate those that bring about protective immune responses, they could use these as antigens (proteins that elicit an immune response) to be used as vaccines in different cancers.

Recently, a research group designed a study that used a tumor mouse model and gathered data on neoepitopes using DNA data and mouse PBMC assays.[1] The researchers introduced two novel tools for neoepitope research. First, they used mathematical modeling to compute differences between immune scores of mutated proteins and their wild-type counterparts. Second, they measured the conformational stability of mutated proteins interacting with the PBMC (MHC1-peptide interactions). These tools identified those neoepitopes that have anchor residues for rigid MHC binding.

The research group went further and demonstrated the power of the information gathered in this study by developing a vaccine that elicited protection against tumor growth in the mouse model. Their study results present opportunities for clinical translation of their tools in human cancer immunotherapy, which has been noticed.[2]

It is an arduous task to identify vaccine-quality neoepitopes from PBMC profiles of cancer patients. Challenges include using neoepitopes that could potentially bring about tolerance or suppression mechanisms into play, for these are mutated self-proteins after all. HemaCare provides PBMC samples including disease state samples such as chronic lymphpcytic leukemia and looks forward to continuing to support cancer research.

References

1: Duan F, et al. Genomic and bioinformatic profiling of mutational neoepitopes reveals new rules to predict anticancer immunogenicity. J Exp Med. 2014 Sep 22.
2: Rita Sullivan King. New rules for anticancer vaccines. http://www.eurekalert.org/pub_releases/2014-09/rup-nrf091714.php 2014 Sep 22.

Topics: Drug Discovery, neoepitope, Vaccine Research, Basic Research

Daisy

Written by Daisy

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